ST266 / Noveome Biotherap - LARVOL DELTA

The novel secretome ST266 activates Akt and protects against oxidative stress-mediated injury in human RPE and Müller cells. (PubMed, Exp Eye Res) - "Herein, we investigated the effect of ST266 on RPE cell injury induced by hydroquinone (HQ), a cigarette smoke related oxidant, hydrogen peroxide (H2O2) and all-trans retinal (atRal), a pro-oxidant component of the retinoid cycle. MK-2206 significantly eliminated ST266-mediated protein phosphorylation of Akt, GSK-3β, and p70S6K and abolished the ST266-protective effect on cell viability. In conclusion, ST266 activates Akt, protects against oxidative stress-mediated cell injury in an Akt-dependent manner, and improves Δψm, suggesting a potential role for ST266 therapy in treating retinal diseases such as AMD."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

ST266-NEC-201: Study to Assess the Safety, Tolerability, and Preliminary Efficacy of ST266 in Infants With Necrotizing Enterocolitis (clinicaltrials.gov) - P1/2 | N=36 | Recruiting | Sponsor: Noveome Biotherapeutics, formerly Stemnion | Trial completion date: Aug 2027 ➔ Nov 2029 | Initiation date: May 2024 ➔ Aug 2024 | Trial primary completion date: Dec 2026 ➔ Jun 2029

Trial completion date • Trial initiation date • Trial primary completion date • Gastrointestinal Disorder • CRP

ST266-NEC-201: Study to Assess the Safety, Tolerability, and Preliminary Efficacy of ST266 in Infants With Necrotizing Enterocolitis (clinicaltrials.gov) - P1/2 | N=36 | Recruiting | Sponsor: Noveome Biotherapeutics, formerly Stemnion | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Disorder • CRP

Study to Assess the Safety, Tolerability, and Preliminary Efficacy of ST266 in Infants With Necrotizing Enterocolitis (clinicaltrials.gov) - P1/2 | N=36 | Not yet recruiting | Sponsor: Noveome Biotherapeutics, formerly Stemnion

New P1/2 trial • Gastrointestinal Disorder • CRP

Human amnionic progenitor cell secretome mitigates the consequence of traumatic optic neuropathy in a mouse model. (PubMed, Mol Ther Methods Clin Dev) - "ST266 treatment effectively downregulated the NLRP3 inflammasome-mediated neuroinflammation pathway after blunt trauma. Overall, treatment with ST266 was shown to improve functional and pathological outcomes in a mouse model of TON, warranting future exploration of ST266 as a cell-free therapeutic candidate for testing in all optic neuropathies."

Journal • Preclinical • CNS Disorders • Inflammation • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain • Vascular Neurology • NLRP3

ST266 Eyedrops for the Treatment of Persistent Corneal Epithelial Defects (clinicaltrials.gov) - P2b | N=8 | Terminated | Sponsor: Noveome Biotherapeutics, formerly Stemnion | N=78 ➔ 8 | Trial completion date: Feb 2023 ➔ Sep 2022 | Active, not recruiting ➔ Terminated; Sponsor undergoing financial hardships - no longer able to support trial; no safety concerns.

Enrollment change • Trial completion date • Trial termination

ST266 Eyedrops for the Treatment of Persistent Corneal Epithelial Defects (clinicaltrials.gov) - P2b | N=78 | Active, not recruiting | Sponsor: Noveome Biotherapeutics, formerly Stemnion | Recruiting ➔ Active, not recruiting

Enrollment closed

The administration of amnion-derived multipotent cell secretome ST266 protects against necrotizing enterocolitis in mice and piglets. (PubMed, Am J Physiol Gastrointest Liver Physiol) - "Strikingly, RNA-seq analysis of the intestinal epithelium in mice reveal the ST266 upregulates critical genes associated with gut remodeling, intestinal immunity, gut differentiation and energy metabolism. These findings show that the amnion-derived secretome ST266 can prevent and treat NEC, suggesting the possibility of novel therapeutic approaches for patients with this devastating disease."

Journal • Preclinical • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • EGF

Study of ST266 Given by Intranasal Delivery in Glaucoma Suspect Subjects (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: Noveome Biotherapeutics, formerly Stemnion | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Glaucoma • Ophthalmology

Safety and Tolerability Study of IV ST266 in COVID-19 Subjects (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Noveome Biotherapeutics, formerly Stemnion | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Inflammation • Novel Coronavirus Disease

The novel secretome ST266 promotes survival of oxidant-stressed human RPE by a mechanism involving the Akt/mTOR/p70S6k/GSK-3b pathway (ARVO 2022) - "When RPE cells were exposed to ST266, Akt phosphorylation increased as well as its downstream targets. ST266 improved cell viability after exposure to various oxidants, an effect that was significantly reduced when Akt activation was blocked. These data suggest that Akt is involved in the mechanism by which ST266 improves cell survival in oxidant-treated human RPE cells."

Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • mTOR

Safety and Tolerability Study of IV ST266 in COVID-19 Subjects (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Noveome Biotherapeutics, formerly Stemnion | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Inflammation • Novel Coronavirus Disease

ST266 Eyedrops for the Treatment of Persistent Corneal Epithelial Defects (clinicaltrials.gov) - P2b | N=72 | Recruiting | Sponsor: Noveome Biotherapeutics, formerly Stemnion | Not yet recruiting ➔ Recruiting | Initiation date: Oct 2021 ➔ Jan 2022

Enrollment open • Trial initiation date

Exploratory Phase II Multicenter, Open-Label, Clinical Trial of ST266, a Novel Secretome for Treatment of Persistent Corneal Epithelial Defects. (PubMed, Transl Vis Sci Technol) - P2 | "In this trial, we found ST266 eye drops might promote corneal epithelization, thereby reducing the PED area, including in refractory cases in a wide range of etiologies. ST266 was well-tolerated by most patients."

Clinical • Journal • P2 data

A Phase 2b Safety and Efficacy Study of ST266 for the Treatment of Persistent Corneal Epithelial Defects (clinicaltrials.gov) - P2b; N=72; Not yet recruiting; Sponsor: Noveome Biotherapeutics, formerly Stemnion

Clinical • New P2b trial

Safety and Tolerability Study of IV ST266 in COVID-19 Subjects (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: Noveome Biotherapeutics, formerly Stemnion; Trial completion date: Oct 2021 ➔ Mar 2022; Trial primary completion date: Oct 2021 ➔ Mar 2022

Trial completion date • Trial primary completion date • Infectious Disease • Inflammation • Novel Coronavirus Disease

Noveome Biotherapeutics, Inc. Commences Phase 1 Clinical Study of ST266 Application for Infectious Disease (including COVID-19) (PRNewswire) - "Noveome Biotherapeutics, Inc. (Noveome) announced that it has commenced its Phase 1 clinical trial by dosing its first patient. This Phase 1 trial is evaluating the safety and tolerability of intravenous (IV) administration of their ST266 product to treat deadly inflammatory responses in COVID-19 patients....The clinical outcome status of ST266-treated patients and the potential effects on clinical laboratory parameters and inflammatory markers will be monitored from baseline through the post-treatment follow-up period."

Trial status • Infectious Disease • Novel Coronavirus Disease

Safety and Tolerability Study of IV ST266 in COVID-19 Subjects (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: Noveome Biotherapeutics, formerly Stemnion; Initiation date: Mar 2021 ➔ May 2021

Clinical • Trial initiation date • Infectious Disease • Inflammation • Novel Coronavirus Disease

[VIRTUAL] ST266 Improves Survival and Mitochondrial Function in Human RPE Cells Under Oxidative Stress (ARVO 2021) - "RPE cells subjected to varied sources of oxidative stress had reduced cell viability and mitochondrial membrane potential. ST266 inhibited these deleterious effects caused by atRal; however, it did not similarly impact the reduction in mitochondrial membrane potential induced by HQ and H2O2. Therefore, the mechanism through which ST266 acts may be oxidant-specific and requires further study."

Age-related Macular Degeneration • Macular Degeneration • Ocular Inflammation • Ophthalmology • Optic Neuritis • Retinal Disorders

Study of ST266 Given by Intranasal Delivery in Glaucoma Suspect Subjects (clinicaltrials.gov) - P1; N=9; Active, not recruiting; Sponsor: Noveome Biotherapeutics, formerly Stemnion; Recruiting ➔ Active, not recruiting; Trial completion date: Apr 2021 ➔ May 2022; Trial primary completion date: Apr 2021 ➔ May 2022

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Glaucoma • Ophthalmology

Safety and Tolerability Study of IV ST266 in COVID-19 Subjects (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: Noveome Biotherapeutics, formerly Stemnion; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease • Novel Coronavirus Disease

The use of amnion-derived cellular cytokine solution for the treatment of gingivitis: A two week safety, dose-ranging, proof-of-principle randomized trial. (PubMed, J Periodontol) - "In this "first in human oral cavity" study, topical ST266 was safe and effective in reducing gingival inflammation in 6 weeks. Longitudinal studies with large sample sizes are warranted to assess the therapeutic value of this novel host modulatory compound in the treatment of periodontal diseases."

Clinical • Journal • Dental Disorders • Immunology • Inflammation • Periodontitis • IFNG • IL1B • IL6 • TNFA

Safety and Tolerability Study of IV ST266 in COVID-19 Subjects (clinicaltrials.gov) - P1; N=12; Not yet recruiting; Sponsor: Noveome Biotherapeutics, formerly Stemnion

Clinical • New P1 trial • Infectious Disease • Novel Coronavirus Disease

Neuroprotection mediated by ST266 requires full complement of proteins secreted by amnion-derived multipotent progenitor cells. (PubMed, PLoS One) - "ST266 fractions below 50kDa increased Schwann cell proliferation in vitro, but were less effective than non-fractionated ST266. Demyelination attenuation was partially associated with the lower molecular weight ST266 fraction, but removal of higher molecular weight biomolecules from ST266 diminishes its neuroprotective effects, suggesting at least some high molecular weight proteins play a role in ST266-mediated neuroprotection."

Journal • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • Ocular Inflammation • Ophthalmology • Optic Neuritis

Amnion-Derived Multipotent Progenitor Cells Suppress Experimental Optic Neuritis and Myelitis. (PubMed, Neurotherapeutics) - "This AMP cell secretome, termed ST266, is a unique biological solution that accumulates in eyes and optic nerves following intranasal delivery, resulting in selective suppression of optic neuritis in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, but not myelitis at the administered dose...Importantly, AMP cells also promote neuroprotective effects in EAE spinal cords, marked by reduced paralysis. Protective effects of systemically administered AMP cells suggest they may serve as a potential novel treatment for multiple sclerosis."

Journal • CNS Disorders • Complement-mediated Rare Disorders • Immunology • Inflammation • Multiple Sclerosis • Ocular Inflammation • Ophthalmology • Optic Neuritis • Thermal Injury