emiplacel (PLX-PAD) / Pluri, Charite - University of Medicine Berlin - LARVOL DELTA

Placenta-Derived Mesenchymal Stromal-Like Cells Promote 3D-Engineered Muscle Tissue Differentiation and Vessel Network Maturation. (PubMed, Small Sci) - "Implantation of a multi-culture system of vascularized human skeletal muscle tissue and PLX-PAD into a rectus abdominal defect in nude mice promoted myocyte differentiation, host vessel penetration, and tissue integration. These findings indicate the ability of placenta-derived cells to induce the formation of vascularized engineered muscle constructs with potential therapeutic applications."

Journal

Cocaine-Induced Microglial Impairment and Its Rehabilitation by PLX-PAD Cell Therapy. (PubMed, Int J Mol Sci) - "These findings highlight the unique role of microglia in modulating cocaine addiction behaviors through their influence on synaptic plasticity and neuronal remodeling associated with memory formation. They also suggest that PLX-PAD therapy may mitigate the detrimental effects of chronic cocaine exposure on microglia, underscoring the importance of incorporating microglia in comprehensive addiction rehabilitation strategies."

Journal • CNS Disorders • Inflammation • Psychiatry

Efficacy, Tolerability and Safety of Intramuscular Injections of PLX PAD for the Treatment of Subjects With Critical Limb Ischemia (CLI) With Minor Tissue Loss Who Are Unsuitable for Revascularization (clinicaltrials.gov) - P3 | N=213 | Completed | Sponsor: Pluristem Ltd. | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Peripheral Arterial Disease

Open-label Multicenter Study to Evaluate the Efficacy of PLX-PAD for the Treatment of COVID-19 (clinicaltrials.gov) - P2 | N=23 | Terminated | Sponsor: Pluristem Ltd. | Phase classification: P2a ➔ P2

Phase classification • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Single Placenta-Derived Mesenchymal-Like Stromal Cell Injection Halts Progression of Primary Knee Osteoarthritis – First Preclinical Results from the PROTO consortium (OARSI 2024) - "Among others, this may be due to the choice of the OA model (primary vs. secondary) and the degree of OA addressed (mild to moderate vs. severe) which do often not match in preclinical and clinical studies. With this study, we test the safety and efficacy of placenta-derived mesenchymal like stromal cells (PLX-PAD) for the treatment of mild-moderate primary OA in the Dunkin Hartley guinea pig model, as a basis for the PROTO consortium clinical trial."

Preclinical • Stroma • Immunology • Osteoarthritis • Pain • Rheumatology

PACE: randomized, controlled, multicentre, multinational, phase III study of PLX-PAD for critical limb ischaemia in patients unsuitable for revascularization: randomized clinical trial. (PubMed, Br J Surg) - P3 | "Although there was no evidence that PLX-PAD reduced amputation-free survival in the entire study population, benefit was observed in patients without diabetes mellitus or whose diabetes was well controlled; this requires confirmation in further studies. Trial registration: NCT03006770 (http://www.clinicaltrials.gov); 2015-005532-18 (EudraCT Clinical Trials register - Search for 2015-005532-18)."

Clinical • Journal • P3 data • Cardiovascular • Diabetes • Metabolic Disorders • Pain

Open-label Multicenter Study to Evaluate the Efficacy of PLX-PAD for the Treatment of COVID-19 (clinicaltrials.gov) - P2a | N=23 | Terminated | Sponsor: Pluristem Ltd. | Active, not recruiting ➔ Terminated; The decision to bring the Study to early clinical readout came in response to COVID-19's evolution as a disease, and the significant changes in the standard of care, leading to an increase in the severity of conditions of the intubated patients.

Trial termination • Infectious Disease • Novel Coronavirus Disease

Double-Blind, Multicenter, Study to Evaluate the Efficacy of PLX PAD for the Treatment of COVID-19 (clinicaltrials.gov) - P2 | N=66 | Terminated | Sponsor: Pluristem Ltd. | Trial completion date: Feb 2023 ➔ Jun 2023 | Active, not recruiting ➔ Terminated; The decision to bring the Study to early clinical readout came in response to COVID-19's evolution as a disease, and the significant changes in the standard of care, leading to an increase in the severity of conditions of the intubated patients

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

Treatment of Muscle Injury Following Arthroplasty for Hip Fracture (HF) (clinicaltrials.gov) - P3 | N=240 | Completed | Sponsor: Pluristem Ltd. | Active, not recruiting ➔ Completed

Trial completion • Musculoskeletal Diseases • Orthopedics

Open-label Multicenter Study to Evaluate the Efficacy of PLX-PAD for the Treatment of COVID-19 (clinicaltrials.gov) - P2a | N=23 | Active, not recruiting | Sponsor: Pluristem Ltd. | Trial completion date: Sep 2022 ➔ Jan 2023

Trial completion date • Infectious Disease • Novel Coronavirus Disease

Double-Blind, Multicenter, Study to Evaluate the Efficacy of PLX PAD for the Treatment of COVID-19 (clinicaltrials.gov) - P2 | N=66 | Active, not recruiting | Sponsor: Pluristem Ltd. | Trial completion date: Jun 2022 ➔ Feb 2023

Trial completion date • Infectious Disease • Novel Coronavirus Disease

Treatment of Muscle Injury Following Arthroplasty for Hip Fracture (HF) (clinicaltrials.gov) - P3 | N=240 | Active, not recruiting | Sponsor: Pluristem Ltd. | Trial completion date: Nov 2023 ➔ Jul 2023

Trial completion date • Musculoskeletal Diseases • Orthopedics

€7.5 Million Granted to Collaborative PROTO Project led by Charité to Study Pluri’s PLX-PAD Cells for Osteoarthritis Treatment (GlobeNewswire) - "Pluri...today announced that a €7.5 million non-dilutive grant from the European Union’s Horizon Europe program has been awarded to PROTO (Advanced PeRsOnalized Therapies for Osteoarthritis)...The goal of the PROTO project is to utilize Pluri’s PLX-PAD cells in a Phase I/IIa study for the treatment of mild to moderate knee osteoarthritis (OA). The project is currently under grant agreement preparation number 101095635. Final approval of the grant is subject to completion of the consortium and Horizon Europe grant agreements."

Financing • CNS Disorders • Osteoarthritis • Pain

Higher Loading of Gold Nanoparticles in PAD Mesenchymal-like Stromal Cells Leads to a Decreased Exocytosis. (PubMed, Cells) - "To this end, we investigated the nanoparticle exocytosis behavior from PLX-PAD cells, a cell type currently in clinical trials as a potential therapeutic agent. We showed that the amount of exocytosed gold from the cells was influenced by the uptake time and loading amount. This observation will facilitate the safe labeling of cells with nanoparticles in the future and contribute to stem cell therapy research."

Journal

Placenta-Derived Mesenchymal-like Adherent Stromal Cells as an Effective Cell Therapy for Cocaine Addiction in a Rat Model. (PubMed, Pharmaceutics) - "We found that PLX-PAD cells attenuated cocaine-seeking behavior through their capacity to migrate to specific mesolimbic regions, homed on the parenchyma in the dentate gyrus of the hippocampus, and restored neurogenesis. We believe that intranasal cell therapy is a safe and effective approach to treating addiction and may offer a novel and efficient approach to rehabilitation."

Journal • Preclinical • CNS Disorders • Psychiatry • Substance Abuse

HIPGEN: a randomized, multicentre phase III study using intramuscular PLacenta-eXpanded stromal cells therapy for recovery following hip fracture arthroplasty : a study design. (PubMed, Bone Jt Open) - "The HIPGEN study assesses the efficacy, safety, and tolerability of intramuscular PLX-PAD administration for the treatment of muscle injury following arthroplasty for hip fracture. It is the first phase III study to investigate the effect of an allogeneic cell therapy on improved mobilization after hip fracture, an aspect which is in sore need of addressing for the improvement in standard of care treatment for patients with FNF. Cite this article: Bone Jt Open 2022;3(4):340-347."

Clinical • Journal • P3 data • Immunology • Musculoskeletal Diseases • Orthopedics

Intramuscular and intratendinous placenta-derived mesenchymal stromal-like cell treatment of a chronic quadriceps tendon rupture. (PubMed, J Cachexia Sarcopenia Muscle) - "Herein, we demonstrate a successfully treated chronic QTR with a synergistic surgical and biological reconstructive treatment approach. This local add-on treatment with PLX-PAD cells may be considered in specific cases of chronic QTRs, not susceptible to traditional suture anchor procedures and which exhibit a high risk of treatment failure. Further scientific engagement is warranted to explore underlying immunomodulatory mechanisms of action behind PLX-PAD cell treatment for tendon injuries."

Journal • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Musculoskeletal Diseases • IL10 • IL6

Treatment of Muscle Injury Following Arthroplasty for Hip Fracture (HF) (clinicaltrials.gov) - P3; N=240; Active, not recruiting; Sponsor: Pluristem Ltd.; Recruiting ➔ Active, not recruiting; Trial completion date: Dec 2021 ➔ Nov 2023; Trial primary completion date: Jun 2021 ➔ May 2022

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Musculoskeletal Diseases • Orthopedics

Double-Blind, Multicenter, Study to Evaluate the Efficacy of PLX PAD for the Treatment of COVID-19 (clinicaltrials.gov) - P2; N=66; Active, not recruiting; Sponsor: Pluristem Ltd.; Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease

Open-label Multicenter Study to Evaluate the Efficacy of PLX-PAD for the Treatment of COVID-19 (clinicaltrials.gov) - P2a; N=23; Active, not recruiting; Sponsor: Pluristem Ltd.; Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease

Pluristem Brings ARDS Associated with COVID-19 Phase II Studies to Clinical Readout (GlobeNewswire) - "Pluristem Therapeutics Inc....is bringing its Acute Respiratory Distress Syndrome (ARDS) associated with COVID-19 Phase II studies to clinical readout. The Company’s COVID-19 program included over 100 patients across two Phase II studies in the U.S., Europe and Israel, and in compassionate use and expanded access programs in the U.S. and Israel. The analysis will be based on 89 patients enrolled in the previously announced two Phase II studies...Company will not pursue...to expand Pluristem’s COVID-19 program to Mexico in collaboration with Innovare R&D. Pluristem expects to announce the topline results of the readout during the fourth quarter of 2021. As part of the clinical readout, Pluristem will examine the safety and efficacy of PLX cells for treating ARDS..."

Clinical data • P2 data • Infectious Disease • Novel Coronavirus Disease

Placenta-Expanded Stromal Cell Therapy in a Rodent Model of Simulated Weightlessness. (PubMed, Cells) - "Clinically relevant, human placenta-derived therapeutic stromal cells (PLX-PAD) are a promising therapeutic alternative...These findings support the therapeutic potential of placenta-derived stromal cells for select physiological deficits during simulated spaceflight. Multiple countermeasures are likely needed for comprehensive protection from the deleterious effects of prolonged spaceflight."

Journal • Preclinical • Muscular Atrophy • Osteoporosis

Pluristem Enters Collaboration With Pharmaceutical Company Innovare R&D to Expand Pluristem’s ARDS Associated With COVID-19 Program to Mexico (GlobeNewswire) - "Pluristem Therapeutics Inc....announced today it has entered into a collaboration agreement with Mexican pharmaceutical company Innovare R&D to expand its ongoing clinical program of PLX cells in the treatment of Acute Respiratory Distress Syndrome (ARDS) associated with COVID-19 in Mexico. The Phase II study in Mexico is subject to the approval of local authorities...In accordance with the agreement, Innovare will open clinical sites and enroll patients for the proposed clinical study in Mexico....Agreement grants Innovare exclusive distribution rights in Mexico to supply PLX cells...All intellectual property and manufacturing rights remain with Pluristem."

Licensing / partnership • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease

Efficacy, Tolerability and Safety of Intramuscular Injections of PLX PAD for the Treatment of Subjects With Critical Limb Ischemia (CLI) With Minor Tissue Loss Who Are Unsuitable for Revascularization (clinicaltrials.gov) - P3; N=213; Active, not recruiting; Sponsor: Pluristem Ltd.; Recruiting ➔ Active, not recruiting; Trial completion date: Mar 2022 ➔ Mar 2021; Trial primary completion date: Dec 2021 ➔ Mar 2021

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

Open-label Multicenter Study to Evaluate the Efficacy of PLX-PAD for the Treatment of COVID-19 (clinicaltrials.gov) - P2a; N=40; Recruiting; Sponsor: Pluristem Ltd.

Clinical • New P2a trial • Infectious Disease • Novel Coronavirus Disease