A Phase 1, Open-Label, Single Center, Dose Escalation Study of the Safety and Pharmacokinetics of mAb AZD5396 and mAb AZD8076 Delivered as dMAbs in Healthy Adults

This is a Phase 1, open-label, single center, dose escalation study to evaluate the safety, tolerability and pharmacokinetic profile of mAb AZD5396 and mAb AZD8076 following delivery of optimized dMAb AZD5396 and dMAb AZD8076 with Hylenex® Recombinant, administered by intramuscular injection (IM) followed immediately by electroporation (EP) using the CELLECTRA™ 2000 with Side Port needle device, in a 2-dose regimen (Days 0 and 3) or a 4-dose regimen (Days 0, 3, 28 and 31) in healthy adults.
The hypothesis is that the administration of dMAb AZD5396 and dMAb AZD8076 will be safe and associated with expression of mAb AZD5396 and mAb AZD8076 in serum.

Start Date19 May 2022

Sponsor / Collaborator

University of Pennsylvania

[+3]

NCT05629923

/ CompletedNot ApplicableIIT

EVALUATION OF COVID-19 VACCINATION EFFICACY AND CONTIXAGEVIMAB-CILGAVIMAB PROPHYLAXIS IN LIVER AND KIDNEY TRANSPLANT PATIENTS: PRELIMINARY STUDY

The goal of this observational study is to evaluate the immune response after COVID-19 vaccination in Liver(LT) and Kidney(KT) transplant recipient. The main question it aims to answer are:
the evaluation of the antibody response after complete vaccination
the efficacy of prophylaxis with long-acting-antibody prophylaxis (LAAB)
All LT and KT patients during follow-up have been enrolled. anti-COVID-19 title was obtained by Electrochemiluminescence Immunoassay (ECLIA) Test(Elyx, Roche). In the case of antibody level <100 IU/ml, patients were invited to prophylaxis with tixagevimab-cilgavimab(AZD7442, AstraZeneca). At three months, a follow-up was performed to assess any COVID-19 infection. At Six months another anti-COVID-19 title is obtained by ECLIA Test(Elyx, Roche) in LT and KT who undergo to LAAB.

Start Date01 Feb 2022

Sponsor / Collaborator

Università degli Studi di Roma Tor Vergata

100 Clinical Results associated with Tixagevimab

100 Translational Medicine associated with Tixagevimab

100 Patents (Medical) associated with Tixagevimab

288

Literatures (Medical) associated with Tixagevimab

01 Jun 2025·CLINICAL MICROBIOLOGY AND INFECTION

Long-term outcomes of passive immunotherapy for COVID-19: a pooled analysis of a large multinational platform randomized clinical trial

Article

Author: Engen, Nicole ; Mena Lora, Alfredo J ; Self, Wesley H ; Williamson, John C ; Price, D Ashley ; Mathews, Gail ; Lundgren, Jens ; Murray, Thomas A ; Kitonsa, Jonathan ; Knox, Daniel B ; Kim, Kami ; Mylonakis, Eleftherios ; Reilly, Cavan ; Siegel, Lianne K ; Young, Barnaby Edward ; Sandkovsky, Uriel ; Jain, Mamta K ; Paredes, Roger ; Ramachandruni, Srikanth ; Holland, Thomas L ; Eriobu, Nnakelu ; Grandits, Gregory A ; Ginde, Adit ; Barkauskas, Christina ; Jensen, Tomas O ; Mourad, Ahmad ; Malin, Jakob J ; Vock, David ; Rapti, Vasiliki ; Higgs, Elizabeth

OBJECTIVES:

Passive immunotherapy, including monoclonal antibodies and neutralizing proteins, was used for the treatment of patients with COVID-19 during the pandemic. Accelerating COVID-19 Therapeutic Interventions and Vaccines-Therapeutics for Inpatients with COVID-19 (ACTIV-3/TICO) was a multinational, randomized placebo-controlled platform trial that evaluated the effectiveness of multiple passive immunotherapy agents in patients hospitalized with COVID-19. Given the long half-life of some agents studied, participants were followed for an extended period to assess the long-term efficacy and sustained safety of these agents.

METHODS:

We conducted a pooled analysis of individual participant data from four trials of ACTIV-3/TICO: sotrovimab, amubarvimab-romlusevimab, tixagevimab-cilgavimab, and ensovibep. Cox proportional hazards models were conducted to compare time to mortality and time to mortality or rehospitalization between participants receiving active agents vs. placebo through 18 months.

RESULTS:

A total of 2311 participants were enrolled between 16 December 2020 and 15 November 2021. Overall, 56.9% (1315/2311) received an active agent and 77.2% (1784/2311) of participants were unvaccinated for SARS-CoV-2. Median duration between symptom onset and enrolment was 8 days (interquartile range, 6-10), and most participants received remdesivir (92.1% [2129/2311]) and corticosteroids (70.4% [1627/2311]) before enrolment. There was no difference in mortality across all active (11.9% [157/1315]) vs. placebo (14.0% [139/996]) arms (hazard ratio, 0.87; 95% CI, 0.70-1.08). Furthermore, there was no difference in combined mortality or rehospitalization across all active (31.7% [417/1315]) vs. placebo (32.1% [320/996]) arms (hazard ratio, 0.96; 95% CI, 0.84-1.10).

DISCUSSION:

In our large study of long half-life passive immunotherapy for hospitalized patients with COVID-19, we did not find evidence of a long-term effect on either mortality or rehospitalization.

TRIAL REGISTRATION:

NCT04501978.

01 May 2025·JOURNAL OF MEDICAL VIROLOGY

Comparative Analysis of Early COVID‐19 Treatment Efficacy in a Multicentric Regional Cohort in Italy: Emulation of a Series of Target Trials

Article

Author: Garattini, Silvia ; D'Abramo, Alessandra ; Mazzotta, Valentina ; Siciliano, Valentina ; Nicastri, Emanuele ; Gavaruzzi, Francesca ; Mastroianni, Claudio M. ; Rosati, Silvia ; Girardi, Enrico ; Lichtner, Miriam ; Falletta, Antonio ; Antinori, Andrea ; Gasperin, Andrea ; Andreoni, Massimo ; Lanini, Simone ; Matteini, Elena ; Milozzi, Eugenia ; Marocco, Raffaella ; Vergori, Alessandra ; Cerva, Carlotta ; Cimaglia, Claudia ; Gramigna, Giulia ; Del Borgo, Cosmo ; Lepri, Alessandro Cozzi ; Rueca, Martina ; Maggi, Fabrizio ; Sarmati, Loredana ; Mastrorosa, Ilaria ; Giannico, Giuseppina ; Torti, Carlo ; Carraro, Anna ; Matusali, Giulia ; Coppola, Luigi ; Fantoni, Massimo ; Meschi, Silvia ; Oliva, Alessandra ; Piselli, Pierluca

ABSTRACT:

Studies comparing all available strategies for the early treatment of mild‐to‐moderate COVID‐19 during the Omicron era are lacking. We included people with mild‐to‐moderate COVID‐19 and at high risk of progressing to severe disease attending five outpatient clinics in Italy over 2022–2023. The primary outcome was the proportion of participants who experienced Day‐30 hospitalization due to COVID‐19 or death. Participants received either nirmatrelvir/ritonavir (NMV/r), molnupiravir (MLP), remdesivir (RDV), sotrovimab (SOT), or tixagevimab/cilgavimab (TIX/CIL). We included 10 038 individuals: females 5052 (50%), median age 71 years (IQR 59–81). In total, 1919 (19%) received SOT, 3732 (37.2%) MLP, 1444 (14%) RDV, 2510 (25%) NMV/r, and 433 (4%) TIX/CIL. Only 1689 (17%) had incomplete vaccination, and 2435 (24.3%) were not immunocompetent. The rate of hospitalization/death was 2.40% (95% CI 2.10–2.71). Unadjusted rates were 0.88% (95% CI 0.55–1.32) for NMV/r, 1.69% (95% CI 1.30–2.15) for MLP, 3.0% (95% CI 1.61–5.08) for TIX/CIL, 3.54% (95% CI 2.76–4.47) for SOT and 5.12% (95% CI 4.05–6.39) for RDV. Weighted analysis showed that NMV/r and MLP were superior to all other interventions. In our population of individuals at high risk of progression to severe disease, there was clinical benefit in using NMV/r or MLP instead of mAbs‐based therapies or RDV.

01 Apr 2025·CTS-Clinical and Translational Science

New Function for Safety Signal Monitoring in MID‐NET^®: The Case of an Anti‐COVID‐19 Drug

Article

Author: Hasegawa, Tomoaki ; Inomata, Satomi ; Okada, Yusuke ; Kinoshita, Yuki ; Watanabe, Kenichi ; Takahashi, Fumitaka ; Ando, Takashi ; Kajiyama, Kazuhiro ; Uyama, Yoshiaki ; Watanabe, Shinya

ABSTRACT:

Real‐world data play a key role in monitoring drug safety at the post‐marketing stage. However, challenges on how to rapidly and continuously obtain analytical results of many outcomes for drug safety signal monitoring still remain. We aimed to establish a rapid and continuous monitoring tool for drug safety assessment based on real‐world data in Japan. An automated process for a new‐user cohort design with customizable analytical conditions was developed. The customizable analytical conditions include exposure and control drugs, 46 outcomes related to liver and kidney functions, blood tests, biomarkers, and time period of interest. Statistical analyses were performed to evaluate the outcome status (present/absent) and calculate the adjusted hazard ratio, with a 95% confidence interval of exposure to control. We monitored the safety signals of an anti‐COVID‐19 drug (combination of tixagevimab and cilgavimab) and compared them with those of two controls (peramivir and the combination of casirivimab and imdevimab) to examine the practical utility of this new tool. Our study provided helpful information (e.g., new safety signals) on many outcomes at multiple time points, which could enhance the understanding of drug safety profiles soon after approval. Our function can be used to rapidly and continuously monitor drug safety signals and contribute to strengthening drug safety monitoring in Japan.

News (Medical) associated with Tixagevimab

08 Apr 2025

·www.astrazeneca.com

AstraZeneca showcases innovation in infectious disease protection at ESCMID Global 2025

AstraZeneca will share new data across its Vaccines & Immune Therapies portfolio at the 2025 Congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global 2025) in Vienna, Austria, from 11-15 April 2025. With 13 abstracts, including two oral presentations and two late-breaking poster presentations, the Company will highlight progress in advancing novel immunisations against bacterial and viral infectious diseases and share real-world evidence showing the burden of respiratory viral infections and the continued need for protection. Benjamin Moutier, Senior Vice President, Vaccines & Immune Therapies, AstraZeneca said: “AstraZeneca is building an innovative portfolio of antibodies and vaccines to tackle two of the top global public health threats – serious bacterial infections and respiratory viral infections. At ESCMID, we’ll share data on three novel monoclonal antibodies targeting high-priority pathogens, highlighting our ambition to redefine care for serious bacterial infections. In addition, we will present 20 years of effectiveness data for Fluenz/FluMist, as well as real-world data highlighting the ongoing burden of RSV and hMPV, two leading causes of respiratory illnesses.” Advancing potential new options for serious bacterial infection prevention and treatment Serious bacterial infections pose significant and growing threats to global health, linked to an estimated 7.7 million deaths a year globally, leading to increasing morbidity and mortality for patients and a substantial burden on health systems.1 At ESCMID, the Company will share preclinical data on investigational monoclonal antibodies (mAbs) targeting three of the top five pathogens identified as urgent risks by the Centers for Disease Control and Prevention: Staphylococcus aureus (S. aureus): Oral presentation on in vivo expression of an mRNA-encoded multi-mechanistic mAb combination against S. aureus. There are millions of methicillin-resistant S. aureus (MRSA) infections annually worldwide, and MRSA is resistant to many types of antibiotics, making treatment highly complex. A pathogen-specific treatment strategy with mAbs targeting some S. aureus virulence factors represents an alternative to broad spectrum antibiotics.2 Pseudomonas aeruginosa (P. aeruginosa): Preclinical data showing that gremubamab, an anti-P. aeruginosa bispecific human mAb, may enhance neutrophil-mediated killing of P. aeruginosa in bronchiectasis patients. P. aeruginosa is a pathogen that colonizes one-third of patients with bronchiectasis, a chronic lung condition impacting about one million people globally and drives significant disease morbidity and mortality.3 Klebsiella pneumoniae (K. pneumoniae): Research on the development and characterisation of bispecific antibodies that protect against bacteraemia and pneumonia from the major serotypes of antibiotic-resistant K. pneumoniae in mouse models. Infections caused by K. pneumoniae are responsible for more than 700,000 yearly deaths worldwide.4 Real-world data examining the impact of respiratory infections AstraZeneca is presenting 20 years of real-world data on Fluenz/FluMist (live attenuated influenza vaccines, LAIV), recently approved in the U.S. as the only vaccine for self- or caregiver administration for the prevention of influenza, demonstrating long-term effectiveness comparable to that of inactivated (IIV) influenza vaccines in children.5 The Company will also present two late-breaking posters featuring real-world studies in patients with haematological malignancies who are highly susceptible to severe respiratory infections. The studies show that outcomes from human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) were similar to those from influenza and COVID-19, highlighting the need for development of novel options for preventing disease caused by hMPV and RSV.6,7 Retrospective analyses from Valencia, Spain, where there is systematic testing for multiple respiratory viruses, highlight the impact of RSV and influenza on severe disease and mortality in older adults throughout the COVID-19 pandemic, and suggest a potentially greater proportion of mechanical ventilation use and in-hospital death from RSV than influenza in adolescents and adults.8,9 Additional real-world data from France highlight the extensive healthcare resource utilisation due to hMPV and RSV and underline the need for routine testing for hMPV to accurately assess its true burden.10 Additionally, data being presented by our partner, Sanofi, confirm the significant public health impact and real-world effectiveness of Beyfortus in reducing RSV disease and hospitalisations in infants.11 Furthering Research in COVID-19 Prevention Data on AZD6563, an investigational novel COVID-19 mRNA vaccine-like particle (VLP) vaccine, demonstrating that a low dose may elicit equivalent cell-mediated immunity to a licensed mRNA vaccine will also be shared.12 Additionally, data will be presented increasing confidence in a SARS-CoV-2 variant-agnostic threshold which could be used as a surrogate endpoint for benchmarking expected efficacy of novel mAbs for the prevention of COVID-19 against emerging variants.13 Key AstraZeneca presentations during ESCMID 2025 Abstract Title Presentation Details Abstract Title Early Science: Serious Bacterial Infections and Respiratory Viral Infections Abstract Title In vivo expression of an mRNA encoded multi-mechanistic mAb combination against Staphylococcus aureus and protection in disease model Presentation Details Oral Presentation Session Title: Around the Lab in 80 Ways: A Journey Through Innovative Therapeutics Date: Saturday 12 April 2025 Time: 11 AM – 12 PM CEST Location: Hall 13 Abstract Title Low dose of a novel SARS-COV-2 mRNA VLP vaccine elicits equivalent cell-mediated immunity to a licensed mRNA vaccine Presentation Details Poster Presentation Session Title: COVID-19 Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title A Bispecific Monoclonal Antibody Targeting Psl and PcrV Enhances Bronchiectasis Patient Neutrophil-Mediated Killing Of Pseudomonas aeruginosa Presentation Details Poster Presentation Session Title: Drug Discovery and New Compounds Mechanisms of Action & Spectrum, Preclinical Data & Basic Pharmacology Date: Sunday 13 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Broad coverage of antibiotic-resistant Klebsiella pneumoniae by multi-specific antibodies against the lipopolysaccharide O-antigen Presentation Details Poster Presentation Session Title: Drug Discovery and New Compounds Mechanisms of Action & Spectrum, Preclinical Data & Basic Pharmacology Date: Sunday 13 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Real-World Evidence: Respiratory Infections Abstract Title Comparative outcomes of hMPV, influenza, and SARS-CoV-2 infections in haematologic malignancy patients: A matched cohort analysis Presentation Details Late-Breaking Poster Presentation Session Title: Outbreaks and Public Health Emergencies Date: Tuesday 15 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Matched cohort study comparing the impact of RSV, influenza, and SARS-CoV-2 infections in patients with haematological malignancies Presentation Details Late-Breaking Poster Presentation Session Title: Outbreaks and Public Health Emergencies Date: Tuesday 15 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Similar proportions and temporal patterns of influenza, RSV, and hMPV among ESKD patients tested between 2020-2023 Presentation Details Poster Presentation Session Title: Influenza and Respiratory Viruses Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Characterization of hMPV and RSV cases in the French national hospital claims database during the 2022-2023 season Presentation Details Poster Presentation Session Title: Influenza and Respiratory Viruses Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Shifting viral landscapes: the impact of SARS-CoV-2 on hospitalization, ICU admission, and mortality in respiratory infections among older adults in Valencia, Spain Presentation Details Poster Presentation Session Title: Influenza and Respiratory Viruses Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Respiratory syncytial virus (RSV)-associated hospitalised influenza-like illness (ILI) and clinical progression in adolescents and adults in Valencia, Spain, 2014/2015-2019/2020: the VALSARI study Presentation Details Poster Presentation Session Title: Influenza and Respiratory Viruses Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Real-world effectiveness of live attenuated (LAIV) and inactivated (IIV) influenza vaccines in children: a systematic literature review (SLR) and network meta-analysis (NMA) Presentation Details Poster Presentation Session Title: Influenza and Respiratory Viruses Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title COVID-19 mAbs Abstract Title Pharmacokinetics and immunogenicity of AZD7442 (Tixagevimab/Cilgavimab) in hospitalised COVID-19 patients: results from the DisCoVeRy trial Presentation Details Oral Presentation Session Title: New developments in prophylaxis and treatment of COVID-19 Date: Saturday 12 April 2025 Time: 11:00 Location: Hall 6 Abstract Title A threshold of protection model for monoclonal antibody pre-exposure prophylaxis against COVID-19 enabling rapid development for future SARS-CoV-2 variants Presentation Details Poster Presentation Session Title: COVID-19 Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Notes AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. References 1. GBD 2019 Antimicrobial Resistance Collaborators. Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2022 Dec 17;400(10369):2221-2248. 2. Tkaczyk C, Newton M et al. In vivo expression of an mRNA encoded multi-mechanistic mAb combination against Staphylococcus aureus and protection in disease model. Oral Presentation. ESCMID Global 2025; Vienna, Austria. 2025. 3. Long MB, Gilmour A et al. A bispecific monoclonal antibody targeting Psl and PcrV enhances bronchiectasis patient neutrophil-mediated killing of Pseudomonas aeruginosa. Poster Presentation #P3642. ESCMID Global 2025; Vienna, Austria. 2025. 4. Doyle M, Smith A et al. Broad coverage of antibiotic-resistant Klebsiella pneumoniae by multi-specific antibodies against the lipopolysaccharide O-antigen. Poster Presentation #P2377. ESCMID Global 2025; Vienna, Austria. 2025. 5. Stuurman AL, Enxing J et al. Real-world effectiveness of live attenuated (LAIV) and inactivated (IIV) influenza vaccines in children: a systematic literature review (SLR) and network meta-analysis (NMA). Poster Presentation #P0120. ESCMID Global 2025; Vienna, Austria. 2025. 6. Salmanton-Garcia J, Marchesi F et al. Comparative outcomes of hMPV, influenza, and SARS-CoV-2 infections in haematologic malignancy patients: a matched cohort analysis. Poster Presentation #P5067. ESCMID Global 2025; Vienna, Austria. 2025. 7. Marchesi F, Salmanton-Garcia J et al. Matched cohort study comparing the impact of RSV, influenza, and SARS-CoV-2 infections in patients with haematologic malignancies. Poster Presentation #P5066. ESCMID Global 2025; Vienna, Austria. 2025. 8. Mira-Iglesias A, Herring T et al. Respiratory syncytial virus (RSV)-associated hospitalisations and clinical progression in adolescents and adults in Valencia, Spain, 2014/2015–2019/2020: the VALSARI study. Poster Presentation #P0131. ESCMID Global 2025; Vienna, Austria. 2025. 9. Mira-Iglesias A, Herring T et al. Respiratory syncytial virus (RSV)-associated hospitalisations and clinical progression in adolescents and adults in Valencia, Spain, 2014/2015–2019/2020: the VALSARI study. Poster Presentation #P0132. ESCMID Global 2025; Vienna, Austria. 2025. 10. Binh Luong Nguyen L, et al. Characterisation of hMPV and RSV hospitalisations in the French national hospital claims database during the 2022-2023 season. Poster Presentation #P0183. ESCMID Global 2025; Vienna, Austria. 2025. 11. Mallah N, Pardo-Seco J, et al. Effectiveness of universal prophylaxis with nirsevimab for prevention of infant hospitalisations due to respiratory syncytial virus : full 2023-24 season analysis of the NIRSE-GAL study. Poster Presentation #P0124. ESCMID Global 2025; Vienna, Austria. 2025. 12. Swanson PA II, Padilla M et al. Low dosage of a novel SARS-COV-2 mRNA VLP vaccine elicits equivalent cell-mediated immunity to a licensed mRNA vaccine. Poster Presentation # P0482. ESCMID Global 2025; Vienna, Austria. 2025. 13. Edge R, Matthews S et al. A validated threshold of protection model for monoclonal antibody pre-exposure prophylaxis against COVID-19 enabling rapid development for future SARS-CoV-2 variants. Poster Presentation #P0448. ESCMID Global 2025; Vienna, Austria. 2025. Corporate and financial

VaccineDrug ApprovalImmunotherapyClinical StudymRNA

14 Mar 2025

·pipelinereview.com

INOVIO Announces Promising Interim Results from Ongoing Proof-of-Concept Clinical Trial of DNA-Encoded Monoclonal Antibodies (DMAbs) for COVID-19

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

Phase 1Clinical Result

13 Mar 2025

·www.prnewswire.com

INOVIO Announces Promising Interim Results from Ongoing Proof-of-Concept Clinical Trial of DNA-Encoded Monoclonal Antibodies (DMAbs) for COVID-19

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., March 13, 2025 /PRNewswire/ -- 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 . Forward-Looking Statements This press release contains certain forward-looking statements relating to INOVIO's business, including the planned publication of data from clinical trials and the potential benefits of INOVIO's DMAb technology platform. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials, product development programs and commercialization activities and outcomes, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines, our ability to support our pipeline of DNA medicine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2023, our Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, and other filings we make from time to time with the Securities and Exchange Commission. There can be no assurance that any product candidate in our pipeline will be successfully developed, manufactured, or commercialized, that the results of clinical trials will be supportive of regulatory approvals required to market products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and we undertake no obligation to update or revise these statements, except as may be required by law. This project was supported by the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) Joint Project Lead for Enabling Biotechnologies (JPL CBRND EB) in collaboration with the Defense Health Agency (DHA) COVID funding initiative for (Phase 1, dose-escalation trial of the safety and pharmacokinetics of SARS-CoV-2 DNA-encoded monoclonal antibodies (DMAb) in healthy adults, The Wistar Institute, Inovio Pharmaceuticals, AstraZeneca, University of Pennsylvania, HR0011-21-9-0001) for this effort. The views expressed in this press release reflect the views of the authors and do not necessarily reflect the position of the Department of the Army, Department of Defense, nor the United States Government. References to non-federal entities do not constitute or imply Department of Defense or Army endorsement of any company or organization. Penn and Dr. Weiner have either received, or may receive in the future, financial consideration related to the licensing of certain Penn intellectual property to INOVIO. Dr. Weiner is a member of the Scientific Advisory Board and Board of Directors for INOVIO. Contacts Media: Jennie Willson, (267) 429-8567, [email protected] Investors: Peter Vozzo - ICR Healthcare, 443-213-0505, [email protected] SOURCE INOVIO Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 1

100 Deals associated with Tixagevimab

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Phase 1	United States	AstraZeneca PLC	19 May 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EULAR2024	Not Applicable	COVID-19 \| Collagen Diseases	90	Tixagevimab and Cilgavimab (Evusheld)	supierkohp(dayfpnyplo) = iebpbjzwrb iaujtonwvf (yodfnnodyk )	Positive	05 Jun 2024
EULAR2024	Not Applicable	COVID-19 \| Collagen Diseases	90	Tixagevimab (Control group (not treated with EVS))	supierkohp(dayfpnyplo) = ockdqtinjq iaujtonwvf (yodfnnodyk )	Positive	05 Jun 2024
ECTRIMS2023	Not Applicable	Multiple Sclerosis anti-CD20 monoclonal antibodies	-	Evusheld	atxanymboa(eaawdrqhot) = Solely four patients (2.08%) developed SARS-CoV-2 infection after Evusheld treatment, presenting with a mild (75%) or moderate (25%) illness. No medical admission was recorded. tfsyhjnpzj (wcccgnokzo ) View more	Positive	30 Sep 2023
EULAR2023	Not Applicable	Collagen Diseases	21	Tixagevimab and Cilgavimab (TGM/CGM)	vcxpyetfrm(flrfhcfgfq) = no COVID-19 related symptoms were observed in the month of follow-up after TGM/CGM administration uzlzpaonbv (uufihggqcf ) View more	-	31 May 2023
ACTRIMS2023	Not Applicable	COVID-19	-	Evusheld 150mg	plexiglzlx(zmewtflhif) = All patients had grade 1 or 2 (mild) severity of COVID-19 wobgtncbhu (hyxfmmweqc ) View more	Positive	30 May 2023
ACTRIMS2023	Not Applicable	COVID-19	-	Evusheld 300mg		Positive	30 May 2023
AAAAI2023	Not Applicable	COVID-19	55	Evusheld	jazwbikxmj(wgsulpnxqn) = all were prescribed oral antivirals vgvxktziqx (wqdqoycfyr ) View more	Positive	01 Feb 2023

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