INNA-051 / Ena Respiratory - LARVOL DELTA

INNA-051 dry powder safety and tolerability study (ANZCTR) - P1 | N=48 | Completed | Sponsor: ENA Respiratory Pty Ltd | Not yet recruiting ➔ Completed | Initiation date: Jul 2024

Trial completion • Trial initiation date • Infectious Disease • Respiratory Diseases

ENA Respiratory Publishes Review of Development of Novel Intranasal Antiviral Host Defense Immune Enhancer INNA-051 in Antiviral Research (GlobeNewswire) - "In the review our Director of Biology, Dr Francesca Mercuri, and her co-authors detail how host-directed therapies could work broadly across a range of viral variants to boost the natural anti-viral defences and help tackle viral respiratory infections. The review goes on to present pre-clinical and clinical data on INNA-051, including data from our Phase 2a proof-of-concept study in an influenza-challenge model, which highlights its potential to protect individuals from illness caused by common and emerging viral respiratory viruses."

Review • Infectious Disease • Influenza

Discovery and development of INNA-051, a TLR2/6 agonist for the prevention of complications resulting from viral respiratory infections. (PubMed, Antiviral Res) - "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 setting."

IO biomarker • Journal • Review • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases • TLR2

Evaluation of intranasal TLR2/6 agonist INNA-051: safety, tolerability and proof of pharmacology. (PubMed, ERJ Open Res) - "INNA-051 increased expression of genes and pathways associated with host defence responses against influenza and was associated with a shorter duration of infection. These studies support further clinical assessment in the context of natural viral respiratory tract infections in individuals at increased risk of severe illness."

Clinical • IO biomarker • Journal • Infectious Disease • Influenza • Respiratory Diseases • TLR2

INNA-051 dry powder safety and tolerability study (ANZCTR) - P1 | N=40 | Not yet recruiting | Sponsor: ENA Respiratory Pty Ltd

New P1 trial • Infectious Disease • Respiratory Diseases

Late Breaking Abstract - INNA-051 prophylaxis enhances innate immune responses confirming accelerated viral clearnace in a human influenza challenge model. (ERS 2023) - "A randomised, placebo-controlled influenza human challenge study was conducted in 123 healthy adults to evaluate the effect of INNA-051 on the course of viral infection and host response. Laboratory-confirmed infected participants with a Heamagglutination Inhibition titre of 10 against A/Perth/16/2009 (H3N2) virus, at time of challenge, were included in the analysis.Host responses to influenza infection, including interferon type I and III gene expression were analyzed using the Nanostring Counter Human Pan Cancer Immune Profiling panel from nasal swabs of INNA-051 treated and placebo treated PCR-confirmed infected participants at D1, 4 and 7 post-viral challenge.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 (Figure 1 A/B, respectively).With the safety profile observed in this study and previously in a Phase 1..."

Late-breaking abstract • Critical care • Infectious Disease • Influenza • Oncology • Respiratory Diseases • TLR2

INNA-051 pre-exposure prophylaxis in a human influenza infection model (ERS 2023) - "This group also demonstrated a significantly lower viral load on Days 6-8 relative to placebo and a trend towards a shorter duration of clinical symptoms. These results in a healthy adult viral challenge study confirm data observed in preclinical challenge models and suggest the potential for a clinical benefit in the setting of natural infection in adults at risk for more severe clinical outcomes.; Endoscopy and interventional pulmonology; Respiratory intensive care; Cell and molecular biology; Public health; General respiratory patient care; Epidemiology"

Critical care • Infectious Disease • Influenza • Respiratory Diseases • TLR2

INNA-051 Influenza Challenge Study (clinicaltrials.gov) - P2a | N=123 | Completed | Sponsor: ENA Respiratory Pty Ltd | Recruiting ➔ Completed

Trial completion • Infectious Disease • Influenza • Respiratory Diseases

Safety and Tolerability of the Toll-Like Receptor (TLR)2/6 Agonist INNA-051 in Healthy Adults (ATS 2022) - "Intranasal INNA-051 was well tolerated up to single doses of 600µg and multiple doses of 300µg. Mild, self-limited nasal adverse events as described are possible indicators of tissue-localized innate immune response by INNA-051. Investigation of cytokine levels and gene expression of the intranasal epithelium are needed to specifically determine TLR2/6 engagement by INNA-051."

Clinical • IO biomarker • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pain • Respiratory Diseases

Development of TLR2/6 Agonist (INNA-051) to Protect the Elderly Against Respiratory Virus Infection (ATS 2022) - "Increased susceptibility of aged mice to lung infection was prevented by robust INNA-051 induced innate immune activation in the URT. This reenforces the critical role of innate immunity in protection from respiratory viral disease in the elderly and supports further clinical development of INNA-051 in human subjects >65 years old."

Clinical • Infectious Disease • Respiratory Diseases • IFNB1

INNA-051 Influenza Challenge Study (clinicaltrials.gov) - P2a | N=123 | Recruiting | Sponsor: ENA Respiratory Pty Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Respiratory Diseases

Intranasal INNA-051 for Prevention of COVID-19 in Adults (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: ENA Respiratory Pty Ltd | N=423 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

INNA-051 Influenza Challenge Study (clinicaltrials.gov) - P2a | N=123 | Not yet recruiting | Sponsor: ENA Respiratory Pty Ltd

New P2a trial • Infectious Disease • Respiratory Diseases

Intranasal INNA-051 for Prevention of COVID-19 in Adults (clinicaltrials.gov) - P2; N=423; Not yet recruiting; Sponsor: ENA Respiratory Pty Ltd

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

ENA Respiratory Begins Phase I Study of COVID-19 Preventative Nasal Spray Designed to Stimulate Body’s Firstline Immune Defense in the Nose (GlobeNewswire) - "ENA Respiratory...has initiated a Phase I human safety study of INNA-051...The Phase I study is a randomized, double-blind and placebo-controlled, single and multiple ascending dose study. Its goal is to investigate the safety and tolerability of INNA-051 in healthy adults ages 18 to 55 years old....INNA-051 reduced viral replication by up to 96 percent....The first two cohorts in the Phase I single ascending dose study have been successfully dosed and the study is expected to be completed by Q3 2021."

Trial completion date • Trial status • Infectious Disease • Novel Coronavirus Disease

ENA Respiratory Advances COVID-19 Preventative Therapy through AU$32 Million Funding Round (GlobeNewswire) - "ENA Respiratory...secured up to AU$32m investment and appointed Ruth Tal-Singer, Ph.D., to its Board of Directors. The new financing will advance INNA-051...The company is poised to initiate its Phase I human safety study of INNA-051 in Australia in the coming weeks. The milestone-based financing round was jointly led by Australian life science investors Brandon Capital Partners and Minderoo Foundation, with co-investment from Uniseed."

Financing • Infectious Disease • Novel Coronavirus Disease

Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model. (PubMed, EBioMedicine) - "The 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."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases