A randomised, double blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of intranasal INNA-051 doses delivered via dry powder spray in adult volunteers

Start Date18 Jul 2024

Sponsor / Collaborator

Ena Respiratory Pty Ltd.

NCT05118763

/ WithdrawnPhase 2

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Efficacy of Intranasal INNA-051 for Prevention of COVID-19 in Adults Following Close Contact With Individuals With SARS-CoV-2 Infection

This is a Phase 2, randomized, double-blind, placebo-controlled study of INNA-051 in adults following household contact with an individual with RT-PCR confirmed SARS CoV-2 infection. This study will evaluate 2 active dose levels of INNA-051 and placebo.

Start Date01 Mar 2022

Sponsor / Collaborator

Ena Respiratory Pty Ltd.

NCT05255822

/ CompletedPhase 2

Phase 2a Study in Healthy Adult Participants Pre-treated With INNA-051 and Challenged With Influenza Virus

This is a Phase 2, randomized, double-blind, placebo-controlled study of INNA-051 in healthy adults, administered prior to administration of an influenza challenge virus. This study will evaluate 2 active dose levels of INNA-051 and placebo.

Start Date28 Feb 2022

Sponsor / Collaborator

Ena Respiratory Pty Ltd.

100 Clinical Results associated with INNA-051

100 Translational Medicine associated with INNA-051

100 Patents (Medical) associated with INNA-051

Literatures (Medical) associated with INNA-051

01 Feb 2025·Antiviral Research

Discovery and development of INNA-051, a TLR2/6 agonist for the prevention of complications resulting from viral respiratory infections

Review

Author: Mercuri, Francesca A ; Anderson, Gary P ; Tal-Singer, Ruth ; Demaison, Christophe ; Miller, Bruce E

Viral respiratory infection is associated with significant morbidity and mortality. The diversity of viruses implicated, coupled with their propensity for mutation, ignited an interest in host-directed antiviral therapies effective across a wide range of viral variants. Toll-like receptors (TLRs) are potential targets for the development of broad-spectrum antivirals given their central role in host immune defenses. Synthetic agonists of TLRs have been shown to boost protective innate immune responses against respiratory viruses. However, clinical success was hindered by short duration of benefit and/or induction of systemic adverse effects. INNA-051, a TLR2/6 agonist, is in development as an intranasal innate immune enhancer for prophylactic treatment in individuals at risk of complications resulting from respiratory viral infections. In vivo animal studies demonstrated the efficacy as prophylaxis against multiple viruses including SARS-CoV-2, influenza, and rhinovirus. Early clinical trials demonstrated an acceptable safety and tolerability profile. Intranasal delivery to the primary site of infection in humans induced a local innate host defense response characterized by innate immune cell infiltration into the nasal epithelium and activation and antiviral response genes. Taken together, the preclinical and clinical data on INNA-051 support further investigation of its use in community infection settings.

01 Jan 2021·EBioMedicineQ1 · MEDICINE

Reducing transmission of SARS-CoV-2 with intranasal prophylaxis

Q1 · MEDICINE

ArticleOA

Author: Stebbing, Justin ; Boiardi, Federico

A review.In a global effort to combat the COVID-19 pandemic, a diverse number of strategies may reduce viral transmission.Non-pharmaceutical interventions (NPIs) slow down epidemic spread without necessarily stopping it.In the absence of a distributed vaccine or highly effective antiviral, NPIs form one of the few readily available tactics we can employ to delay and/or reduce the spread.NPIs, however, have no influence on ones immunity to SARS-CoV-2, which is attained in one of two ways-infection, or immunization.As SARSCoV-2 infection probably does not result in lifelong immunity, the necessity for a therapy that might prevent transmission is of importance.INNA-051 is a synthetic antiviral that stimulates the innate immune system, also by binding to TLR-2 on the mucosa of airway epithelial cells.In the study, 24 female ferrets were split into 4 groups of 6.Groups 1 and 2 received different i.n. doses of INNA-051, group 3 received a mixed i.n. dose of INNA-051 and phosphate-buffered saline (PBS), and group 4 (the control group) received i.n. PBS 4 days prior to an i.n. SARS-CoV-2 challenge.The ferrets were then inoculated with SARS-CoV-2.No adverse reactions were seen during this period.At 5 days post-challenge (pc), all INNA-051-treated groups had reduced viral RNA levels (>10-fold in comparison to the control group).Beyond 10 days pc, levels of viral RNA were below the limit of quantification in all treatment groups.INNA-051-treated groups were combined into a single data set and then compared to the control group.Group 2, having received two 1 mL doses at 20 mg/mL (low dose), demonstrated the most favorable results.There was a 96% and 93% virus reduction in throat swabs and nasal washes, resp., compared to untreated ferrets (P < 0.0001 and P = 0.0107).Such pos. results in a ferret model may be indicative of the antivirals potential success in human trials.Like humans, ferrets express the metallopeptidase entry receptor for the virus, angiotensin-converting enzyme 2 (ACE2).These findings exemplify an encouraging potential for intranasal treatments to combat transmission and initial infection of SARS-CoV-2.Such an advance would be most beneficial for those that have an elevated risk of acquiring infection, such as elderly residents living in close communities, ie, those who are both susceptible and vulnerable.At the very least, the notion of intranasal prophylaxis has exhibited the potential to open doors to promising innovative paths for forthcoming investigation.

01 Jan 2021·EBioMedicineQ1 · MEDICINE

Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model

Q1 · MEDICINE

ArticleOA

Author: Vanessa Lucas ; Gillian S. Slack ; Pamela C. Proud ; Breeze E. Cavell ; Francesca Mercuri ; Weiguang Zeng ; Brendon Y. Chua ; Kathryn A. Ryan ; Ian Holmes ; Kevin R. Bewley ; Stuart Dowall ; David C. Jackson ; Marilyn J. Aram ; Nathan W. Bartlett ; Robert J. Watson ; Nadina I. Wand ; Susan A. Fotheringham ; Didier Ngabo ; Daphne Tsitoura ; Emma Rayner ; Paul Yeates ; Rebecca Cobb ; Stephen Thomas ; Christophe Demaison ; Catherine M.K. Ho ; Miles W. Carroll

BACKGROUNDThe novel human coronavirus SARS-CoV-2 is a major ongoing global threat with huge economic burden. Like all respiratory viruses, SARS-CoV-2 initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission.METHODSSARS-CoV-2 Victoria/01/2020 was passaged in Vero/hSLAM cells and virus titre determined by plaque assay. Challenge virus was delivered by intranasal instillation to female ferrets at 5.0 × 10⁶ pfu/ml. Treatment groups received intranasal INNA-051, developed by Ena Respiratory. SARS-CoV-2 RNA was detected using the 2019-nCoV CDC RUO Kit and QuantStudio™ 7 Flex Real-Time PCR System. Histopathological analysis was performed using cut tissues stained with haematoxylin and eosin (H&E).FINDINGSWe show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. After 5 days post-exposure to SARS-CoV-2, INNA-051 significantly reduced virus in throat swabs (p=<0.0001) by up to a 24 fold (96% reduction) and in nasal wash (p=0.0107) up to a 15 fold (93% reduction) in comparison to untreated animals.INTERPRETATIONThe results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT, to reduce SARS-CoV-2 transmission and provide protection against COVID-19.FUNDINGThis work was funded by Ena Respiratory, Melbourne, Australia.

News (Medical) associated with INNA-051

09 Apr 2025

·www.globenewswire.com

ENA Respiratory Partners with University of Maryland and Leading Respiratory Disease Expert to Conduct Phase 2 Study of INNA-051 Antiviral Host Defence Enhancer

Phase 2 to evaluate safety, tolerability and efficacy of INNA-051 in the prevention of illness due to viral respiratory infectionsStudy to be led by global health physician scientist, Dr. Justin Ortiz, Professor of Medicine at the University of Maryland School of Medicine MELBOURNE, Australia, April 09, 2025 (GLOBE NEWSWIRE) -- ENA Respiratory, a clinical-stage pharmaceutical company developing antiviral host defence enhancers to minimize the impact of viral respiratory infections, announces today that it has secured the University of Maryland’s renowned global health institution, CVDGH, as clinical partner to conduct a Phase 2 proof of concept study of INNA-051. Dr. Justin Ortiz, Professor of Medicine at the University of Maryland School of Medicine’s Center for Vaccine and Global Development (CVD) and a global health physician scientist with expertise in respiratory virus protection and control will be Principal Investigator. INNA-051 is being developed as a convenient, once-a-week nasal dry powder product to reduce the impact of viral respiratory infections and prevent severe complications in at-risk populations, including the elderly, those with an underlying medical condition and individuals with occupational risk such first responders, military or essential services personnel. The study will be a randomized, double-blind, placebo-controlled, multicenter, study of INNA-051 in generally healthy adult participants who are at increased risk to viral respiratory infections during the North American 2025/26 fall/winter season. Top line data is anticipated in Q3 2026. “Partnering with CVD and having Professor Justin Ortiz as one of the Principal Investigators for this Phase 2 trial is a significant step for ENA Respiratory,” said Christophe Demaison, PhD CEO of ENA Respiratory. “The esteemed team at the University of Maryland School of Medicine, led by Professor Justin Ortiz alongside colleagues Professor Kirsten Lyke and Dr. Meagan Deming, brings extensive experience and a proven track record in conducting similar trials. We now look forward to working together to deliver the next step in the development of what we believe could be a significant new approach to reducing the enormous burden of respiratory viral diseases.” Dr. Justin Ortiz, Principal Investigator, said: “Viral respiratory infections are a major global public health problem and there is a clear need for new approaches to tackle the complications that lead to significant morbidity and mortality. We are excited to be partnering with ENA Respiratory on this important study to test their new approach for boosting the body’s natural host defence pathways.” Note: Dr. Ortiz previously served as a paid scientific advisor for ENA Respiratory, but he no longer maintains any financial relationship beyond funding for research. About ENA Respiratory ENA Respiratory is a clinical-stage pharmaceutical company tackling respiratory viral infections through the development of host defence enhancers which locally prime and boost the body’s natural first line of defence against invading pathogens. Being virus-agnostic, ENA’s approach offers a solution to protect against common and emerging respiratory viruses for which vaccines or direct-acting antivirals have limitations or do not exist. The company’s lead product, INNA-051, is being developed as a convenient, once-a-week nasal dry powder product to reduce the impact of viral respiratory infections and prevent severe complications in at-risk populations, including the elderly, those with an underlying medical condition (including chronic lung conditions, diabetes, kidney disease, and cardiovascular disease) and individuals with occupational risk (e.g. first responders, military or essential services personnel). INNA-051 is a potent agonist of toll-like receptor 2/6 (TLR2/6) which plays a key role in recognising pathogens and potentiating innate immune responses. With a safety profile supporting seasonal prophylaxis use, it has demonstrated accelerated virus clearance and stimulation of antiviral host defences, including IFN Type I & III responses, in a Phase IIa proof-of-principle study using a human influenza-challenge model. Headquartered in Melbourne, Australia, the company has raised US$33 million (AU$46 million) in financing from Brandon Capital, The Minderoo Foundation, Flu Lab and Uniseed. It is partnered with the US COPD Foundation to support patient-centered clinical development of INNA-051 in COPD and has been awarded a US$13.1 million contract from the U.S. Department of Defense. It is an alumni member of BLUE KNIGHT™, a joint initiative between Johnson & Johnson Innovation and BARDA designed to accelerate novel potential solutions for future pandemics. For more information, please visit https://enarespiratory.com Follow us on LinkedIn. For further information please contact: Media – Australia Kirrily Davis, E: kdavis@bcpvc.com M: +61 (0)401 220228 Media – International Charles Consultants Sue Charles, E: sue.charles@charles-consultants.com M: +44 (0)7968 726585 Chris Gardner, E: Chris@CGComms.onmicrosoft.com M: +44 (0)7956 031077

Phase 2

12 Feb 2025

·www.globenewswire.com

ENA Respiratory Receives US$5m Investment from Flu Lab to Support Clinical Development of Novel Intranasal Antiviral Host Defence Immune Enhancer, INNA-051

Feb. 10, 2025 -- ENA Respiratory, a clinical-stage pharmaceutical company developing antiviral host defence immune enhancers to minimize the impact of viral respiratory infections, announces today it has received a US$5 million investment from Flu Lab. Flu Lab, a California-based organization founded to advance innovative approaches for the prevention and treatment of influenza, provided the funding to support ENA’s clinical development of INNA-051. A simple to administer, virus-agnostic, seasonally delivered product designed to minimize the impact of viral respiratory infections. It addresses the limitations of current vaccine and direct-acting antiviral approaches and could provide a critical advancement in reducing the continued impact of common and emerging respiratory viruses, such as influenza, on vulnerable populations and the healthcare system. INNA-051 is a host defence immune enhancer which locally primes and boosts the body’s innate immune response – the natural first line of defence. It is being developed as a convenient, once-a-week nasal dry powder product to reduce the impact of viral respiratory infections and prevent severe complications in at-risk populations, including the elderly, those with an underlying medical condition (including chronic lung conditions, diabetes, kidney disease, and cardiovascular disease) and individuals with occupational risk (e.g. first responders, military or essential services personnel). The Flu Lab investment will support ENA’s planned Phase II proof-of-concept community infection study to assess the safety and potential efficacy of INNA-051 in reducing the incidence and duration of symptomatic infections caused by common respiratory viruses, including seasonal influenza, coronaviruses, rhinovirus, respiratory syncytial virus and human metapneumovirus, in young adults at risk for exposure living in the US. ENA Respiratory’s CEO Christophe Demaison, PhD, said: “There is an urgent need for new approaches to reduce the enormous burden of serious viral respiratory infections including influenza, and this investment from Flu Lab will allow us to accelerate our clinical program. We are delighted to have Flu Lab’s support and believe it is a strong endorsement of the work we have done to date in developing INNA-051 and its potential to make a meaningful difference in reducing mortality and morbidity.” ENA Respiratory is a clinical-stage pharmaceutical company tackling respiratory viral infections through the development of host defence immune enhancers which locally prime and boost the body’s innate immune response – the natural first line of defence against invading pathogens. Being virus-agnostic, ENA’s antiviral host defence enhancers offer solutions to protect against common and emerging respiratory viruses for which vaccines or direct-acting antivirals have limitations or do not exist. The company’s lead product, INNA-051, is being developed as a convenient, once-a-week nasal dry powder product to reduce the impact of viral respiratory infections and prevent severe complications in at-risk populations, including the elderly, those with an underlying medical condition (including chronic lung conditions, diabetes, kidney disease, and cardiovascular disease) and individuals with occupational risk (e.g. first responders, military or essential services personnel). INNA-051 is a potent agonist of toll-like receptor 2/6 (TLR2/6) which plays a key role in recognising pathogens and potentiating innate immune responses. With a safety profile supporting seasonal prophylaxis use, it has demonstrated accelerated virus clearance and stimulation of antiviral host defences, including IFN Type I & III responses, in a Phase IIa proof-of-principle study using a human influenza-challenge model. Headquartered in Melbourne, Australia, the company has raised US$33 million (AU$46 million) in financing from Brandon Capital, The Minderoo Foundation, Flu Lab and Uniseed. It is partnered with the US COPD Foundation to support the clinical development of INNA-051 in COPD and has been awarded a US$13.1 million contract from the U.S. Department of Defense. It is an alumni member of BLUE KNIGHT™, a joint initiative between Johnson & Johnson Innovation and BARDA designed to accelerate novel potential solutions for future pandemics. The content above comes from the network. if any infringement, please contact us to modify.

Immunotherapy

18 Dec 2024

·www.globenewswire.com

ENA Respiratory Announces Peer-Reviewed Publication of First Time in Humans and Influenza Virus Challenge Studies with the Intranasal Innate Immunomodulator INNA-051

When compared to placebo, prophylactic administration of INNA-051 was associated with significantly increased expression of multiple host defense genes and shorter duration of infection in influenza virus-infected individuals.Data published in ERJ Open Research, a leading open access journal in respiratory medicine. MELBOURNE, Australia, Dec. 18, 2024 (GLOBE NEWSWIRE) -- ENA Respiratory, a clinical-stage pharmaceutical company developing innate immune modulators for the prevention of complications associated with respiratory viral infections in at-risk populations, announces today the publication of results of its Phase IIa proof-of-principle study with its liquid formulation of INNA-051 in ERJ Open Research, a leading research journal of the European Respiratory Society1. The publication also includes data from ENA Respiratory’s dose-escalation study to assess tolerability and mechanistic biomarkers following single and repeated intranasal administrations of INNA-051 in individuals aged 18-55. Headline results of the challenge study, conducted in the UK in 123 healthy volunteers were first announced in February 2023 with further analyses announced in September 2023. A virus-agnostic intranasal host defence immunomodulator, INNA-051, is a potent first-in-class agonist of toll-like receptor 2/6 (TLR2/6) which plays a key role in recognizing pathogens and triggering the innate immune response. The data presented in the publication demonstrate: INNA-051 was well tolerated in both studies, with no dose-limiting toxicities identified.Mechanistic biomarkers assessed in both studies demonstrated the expected engagement of pharmacology, including innate immune pathways.Post hoc analysis conducted in laboratory-confirmed infected participants with low or no antibody titre against the challenge virus showed INNA-051 treatment led to significantly shorter duration of infection and increased expression of genes and pathways associated with host defence responses against influenza. ENA Respiratory’s CEO, Christophe Demaison, PhD, said: “The publication of the results of these studies demonstrates the strength of the data supporting our continued development of INNA-051 as a potentially significant new approach to protecting people at risk of real harm from serious respiratory viral infections. INNA-051 is designed to boost the body’s innate immune response – the natural first line of defence – directly at the site of infection and prevent complications relating to infection by common respiratory viruses or emerging new viruses. The newly published data confirm pre-clinical data demonstrating that INNA-051 is well-tolerated and primes virus-agnostic local innate immune responses that boost host defence pathways.” The results of the publication announced today supported continued development of INNA-051 and the planned Phase II study to assess the potential of INNA-051 to prevent symptomatic viral respiratory infections in a community setting. ENA is completing a Phase 1b study of a dry powder formulation of INNA-051 with an anticipated shelf life of over two years at room temperature. Headline data demonstrated an acceptable safety profile and evidence of local activation of innate immune pathways in older adults. Results will be announced early in 2025. 1. ERJ Open Res 2024 Dec 9;10(6):00199-2024. doi: 10.1183/23120541.00199-2024 About ENA Respiratory ENA Respiratory is a clinical-stage pharmaceutical company tackling serious respiratory viral infections through the development of host defence immune modulators which locally prime and boost the body’s innate immune response – the natural first line of defence. Being virus-agnostic, immune enhancers are complementary to often virus-specific vaccines and existing direct-acting antivirals. The company’s lead product, INNA-051, is a potent agonist of toll-like receptor 2/6 (TLR2/6) which plays a key role in recognising pathogens and triggering the innate immune response. With a safe profile supporting seasonal prophylaxis use, it has demonstrated accelerated virus clearance and stimulation of antiviral host defences, including IFN Type I & III responses, in a Phase IIa proof-of-principle study using a human influenza-challenge model (ERJ Open Res 2024 Dec 9;10(6):00199-2024). INNA-051 is being developed as a convenient, once-a-week nasal dry powder product to prevent complications associated with respiratory viral infections in at-risk populations, including the elderly, those with an underlying medical condition (including chronic lung conditions, diabetes, kidney disease, and cardiovascular disease) and individuals with occupational risk (e.g. first responders, military or essential services personnel). Headquartered in Melbourne, Australia, the company has raised US$26M (AU$44million) in equity financing from Brandon Capital, The Minderoo Foundation and Uniseed. It is partnered with the US COPD Foundation to support the clinical development of INNA-051 in COPD and has been awarded a US$13.1 million contract from the U.S. Department of Defense. It is an alumni member of BLUE KNIGHT™, a joint initiative between Johnson & Johnson Innovation and BARDA designed to accelerate novel potential solutions for future pandemics. For more information, please visit https://enarespiratory.com Follow us on LinkedIn: https://www.linkedin.com/company/enarespiratory-pty-ltd/ For further information please contact: Media – Australia Kirrily Davis, E: kdavis@bcpvc.com M: +61 (0)401 220228 Media – International Charles Consultants Sue Charles, E: sue.charles@charles-consultants.com M: +44 (0)7968 726585 Chris Gardner, E: Chris@CGComms.onmicrosoft.com M: +44 (0)7956 031077

Phase 2ImmunotherapyPhase 1Clinical Result

100 Deals associated with INNA-051

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Phase 2	-	Ena Respiratory Pty Ltd.	01 Mar 2022
Influenza, Human	Preclinical	United Kingdom	Ena Respiratory Pty Ltd.	28 Feb 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


GlobeNewswire Manual	Phase 1	Viral respiratory infection	-	INNA-051	(qfiteegips) = Biomarker analysis showed that INNA-051 triggered host defence pathways within eight hours of each dose. iakcgoxyal (mpxegqwdvt ) View more	Positive	02 Apr 2025
GlobeNewswire Manual	Phase 1	Viral respiratory infection	-	Placebo		Positive	02 Apr 2025
NCT05255822 (ERS2023) Manual	Phase 2	Influenza, Human	123	INNA-051	(sqjbvwhzwa) = INNA-051 was found to increase host responses against influenza and interferon type I & III gene expression compared to placebo treatment, reflecting accelerated viral clearance observed in this study dvoocvucms (emejneqfzb )	Positive	11 Sep 2023

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