INI-4001 / Inimmune - LARVOL DELTA

A TRAC-478-adjuvanted recombinant N1 neuraminidase influenza virus vaccine induces balanced and broadly protective immune responses. (PubMed, NPJ Vaccines) - "We evaluated an intramuscular recombinant neuraminidase vaccine (N1-MPP) adjuvanted with a lipidated toll-like receptor (TLR)7/8 agonist (INI-4001), a synthetic TLR4 agonist (INI-2002), or both (TRAC-478) delivered as aqueous, liposomal, or squalene oil-in-water emulsions in mice...Aqueous and emulsion TRAC-478 N1-MPP induced high titers of cross-reactive, functional antibodies that exhibited strong ADCC activity and conferred protection in passive-transfer experiments. TRAC-478 N1-MPP vaccination protected against both H5N1 clade 1 and clade 2.3.4.4b viruses and recent H1N1 isolates, supporting the further development of N1-MPP adjuvanted with TRAC-478 emulsion as a stand-alone vaccine or potentially as a supplement for current vaccination regimens to improve protection against both seasonal influenza virus and strains with pandemic potential."

Journal • Infectious Disease • Influenza • Respiratory Diseases • CD4 • TLR4

Trial of INI-4001 in Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Inimmune Corporation | Not yet recruiting ➔ Recruiting | Trial completion date: Apr 2026 ➔ Mar 2027 | Trial primary completion date: Aug 2024 ➔ Oct 2026

Enrollment open • Trial completion date • Trial primary completion date • Solid Tumor

Generation of a shelf-stable, broadly-reactive influenza vaccine formulated with TLR4, TLR7/8, or TLR9 stimulating adjuvants. (PubMed, Vaccine) - "Influenza H1 and H3 hemagglutinin proteins based upon the computationally-optimized broadly-reactive antigen (COBRA) methodology were mixed with one of three toll-like receptor (TLR) agonists, CpG1826 (TLR9 agonist), INI-2002 (TLR4 agonist), or INI-4001 (TLR7/8 agonist)...However, all vaccinated ferrets from these groups were protected against an H1N1 influenza virus challenge, irrespective of the adjuvant. Overall, the constituted vaccines used following the TFF process were effective at eliciting protective immune responses following intranasal administration to ferrets."

Journal • Infectious Disease • Influenza • Respiratory Diseases • TLR4 • TLR7 • TLR9

Elicitation of protective immune responses against influenza a viruses in elderly ferrets by adjuvanted recombinant universal influenza hemagglutinin vaccines. (PubMed, Immun Ageing) - "These COBRA vaccines were mixed with either TRAC478, which is a combination of two TLR agonists, INI-2002 (a synthetic TLR4 agonist) and INI-4001 (a synthetic TLR7/8 agonist), or SAS, which is a mixture of INI-2002 and a semi-synthetic saponin...In addition, there were reduced viral titers detected in nasal washes compared to elderly ferrets vaccinated with unadjuvanted HA proteins. Overall, both TRAC478 and SAS were effective adjuvants to enhance protective antibodies in elderly ferrets compared to animals that were vaccinated with only COBRA HA protein."

Journal • Infectious Disease • Influenza • Respiratory Diseases • TLR4

The TLR7/8 agonist INI-4001 enhances the immunogenicity of a Powassan virus-like-particle vaccine. (PubMed, NPJ Vaccines) - "Lastly, we show that the protection elicited by INI-4001 adjuvanted POW-VLP vaccine is unaffected by either CD4+ or CD8+ T cell depletion and can be passively transferred to unvaccinated mice indicating that protection is mediated through humoral immunity. This study highlights the utility of novel synthetic adjuvants in VLP-based vaccines."

Journal • Infectious Disease • CD4 • CD8 • TLR4

Encapsulation of the lipidated TLR7/8 agonist INI-4001 into ionic liposomes impacts H7 influenza antigen-specific immune responses. (PubMed, Drug Deliv Transl Res) - No abstract available

Journal • Infectious Disease • Influenza • Respiratory Diseases

A first-in-human phase 1 clinical trial of INI-4001, a novel TLR7/8 agonist, in patients with advanced solid tumors. (ASCO 2025) - P1 | "INI-4001 may continue as monotherapy or combination as long as the subject receives benefit. Following cessation of INI-4001, patients will be requested to participate in long-term follow-up to assess overall survival."

Clinical • Metastases • P1 data • Lung Cancer • Oncology • Solid Tumor

A novel cationic liposome-formulated toll like receptor (TLR)7/8 agonist enhances the efficacy of a vaccine against fentanyl toxicity. (PubMed, J Control Release) - "Fentanyl vaccines adjuvanted with either cationic INI-4001 liposomes or the aqueous INI-4001 adsorbed to alum induced significant surface expression of co-stimulatory molecules and maturation markers in a murine dendritic cell line (JAWS II), while the former was superior in enhancing the macrophages surface expression of CD40, CD86 and inducible nitric oxide synthase (iNOS), indicative of maturation and activation. These results warrant further investigation of liposome-based formulations of TLR7/8 agonists for improving the efficacy of vaccines targeting F/FA and other opioids of public health interest."

IO biomarker • Journal • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Depression • Infectious Disease • Psychiatry • Substance Abuse • CD40 • CD86

A cationic liposome-formulated Toll Like Receptor (TLR)7/8 agonist enhances the efficacy of a vaccine against fentanyl toxicity. (PubMed, bioRxiv) - "Fentanyl vaccines adjuvanted with either cationic INI-4001 liposomes or the aqueous INI-4001 adsorbed to alum induced significant surface expression of co-stimulatory molecules and maturation markers in a murine dendritic cell line (JAWS II), while the former was superior in enhancing the macrophages surface expression of CD40, CD86 and inducible nitric oxide synthase (iNOS), indicative of maturation and activation. These results warrant further investigation of liposome-based formulations of TLR7/8 agonists for improving the efficacy of vaccines targeting F/FA and other opioids of public health interest."

IO biomarker • Journal • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Depression • Infectious Disease • Psychiatry • Substance Abuse • CD40 • CD86

The TLR7/8 agonist INI-4001 enhances the immunogenicity of a Powassan virus-like-particle vaccine. (PubMed, bioRxiv) - "We further show that this protection is mediated by a humoral immune response which is both broader and more durable than a POW-VLP vaccine formulated with alum. These findings demonstrate the effectiveness of the novel synthetic TLR7/8 agonist INI-4001 as an adjuvant for low-dose VLP-based vaccines and the ability of this vaccine platform to improve upon current tick-borne flavivirus vaccine methodology."

Journal • Infectious Disease • CD4 • CD8 • TLR4

INIMMUNE ANNOUNCES FIRST CANCER PATIENT DOSED IN PHASE 1 CLINICAL STUDY USING THE IMMUNOTHERAPEUTIC INI-4001, A NOVEL TLR7/8 AGONIST (PRNewswire) - "Inimmune...announced today the dosing of the first patient in its Phase 1 single ascending dose study of INI-4001 in patients with advanced solid tumors. This is an open-label, multiple-ascending dose, two-part dose ranging and cohort expansion study of INI-4001 in patients with advanced solid tumors. This first-in-human trial of INI-4001...will consist of two parts. In Phase 1a, single dose escalation cohorts receiving monotherapy INI-4001 will determine PK, safety, and tolerability. This is followed by Phase 1b where patients who have progressed or have stable disease after 3 cycles of INI-4001 will be allowed to receive concurrent administration of an anti-PD-1 or anti-PD-L1 immunotherapy plus INI-4001....Inimmune's trial of INI-4001 is being conducted in Australia and is expected to be complete by the end of 2025."

Trial completion date • Trial status • Solid Tumor

Mechanistic insights into the cellular and molecular mechanisms of an anti-opioid vaccine formulated with a novel Toll-Like receptor (TLR) 7/8 agonist (IMMUNOLOGY 2024) - "Our novel lipidated adjuvant INI-4001 which engages TLR 7/8 signaling on innate immune cells was shown to significantly enhance the immunogenicity and efficacy of an anti-fentanyl vaccine in blocking fentanyl induced-antinociception, respiratory and cardiovascular depression in rodents. We applied in vivo and in vitro flow cytometry-based assays to decipher innate immune response and B cell responses associated with adjuvanted fentanyl vaccine formulation. Kinetics of innate immune response post vaccination at the site of injection (muscle) and draining lymph nodes were tracked, as well as the maturation and the activation status of multiple dendritic cell (DC) subsets and other cells, to identify early molecular signatures of vaccine efficacy."

Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Depression • Psychiatry • Substance Abuse

Trial of INI-4001 in Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=50 | Not yet recruiting | Sponsor: Inimmune Corporation

Metastases • New P1 trial • Oncology • Solid Tumor