avoplacel (PLX-R18) / Pluri - LARVOL DELTA

Pluri Announces Exclusive Collaboration Agreement with Hemafund to Enhance Ukraine’s Radiation Emergency Preparedness (GlobeNewswire) - "Pluri Inc...today announced that it has signed an exclusive collaboration agreement with Hemafund Ltd...This Collaboration aims to establish a strategic initiative for stockpiling, distribution, and potential clinical advancement of Pluri’s innovative PLX-R18 cell therapy ('PLX-R18') as a countermeasure against Hematopoietic Acute Radiation Syndrome ('H-ARS') in Ukraine. Subject to certain conditions, the Collaboration Agreement will be effective for an initial period of three years and can be extended by the parties for an additional period of three years. Pursuant to the Collaboration Agreement, Pluri will produce and supply PLX-R18 as a potential treatment for H-ARS following nuclear radiation exposure...As part of this Collaboration, Pluri and Hemafund will work toward securing external funding to build an initial capacity of 12,000 doses of PLX-R18, ensuring preparedness for radiation-related emergencies."

Commercial • Hematological Disorders

Pluri’s PLX-R18 Increases Blood Cell Counts and Reduces Need for Transfusions in a Phase I Study: Results Published in Nature Bone Marrow Transplantation (Nasdaq) - "Dr. Joseph P. McGuirk...'This study suggested that PLX-R18 was able to increase blood cell counts and reduce the need for transfusions regardless of whether or not patients received hematopoietic growth factors, strengthening our conclusion that it was indeed PLX-R18, and not the other medications given to the patients, which contributed to the demonstrated efficacy. PLX-R18 shows promise in improving incomplete hematopoietic recovery post-HCT and has potential in other condition where cytopenia is a problem, for example, after CAR-T therapy.'"

Media quote

Pluri’s PLX-R18 Increases Blood Cell Counts and Reduces Need for Transfusions in a Phase I Study: Results Published in Nature Bone Marrow Transplantation (GlobeNewswire) - P1 | N=21 | NCT03002519 | Sponsor: Pluristem Ltd. | "Pluri...today announced the publication of an article titled “Placental expanded mesenchymal-like cells (PLX-R18) for poor graft function after hematopoietic cell transplantation: A phase I study” in the peer reviewed journal Nature Bone Marrow Transplantation....As described in the article, in a successful Phase I first-in-human study which achieved its primary endpoint, patients with incomplete hematopoietic recovery post-hematopoietic cell transplantation (HCT) were treated with escalating doses of Pluri’s cell therapy, PLX-R18....'These results reinforce PLX-R18’s role as a potent potential therapy for hematological disorders, encompassing its proposed application in treating acute radiation syndrome.'"

P1 data • Bone Marrow Transplantation • Transplantation

Placental expanded mesenchymal-like cells (PLX-R18) for poor graft function after hematopoietic cell transplantation: A phase I study. (PubMed, Bone Marrow Transplant) - P1 | "Likewise, red blood cell transfusions decreased from 2.91 units/month at baseline to 0 at month 12 (p = 0.0005). PLX-R18 was safe and well tolerated and shows promise in improving incomplete hematopoietic recovery post-HCT."

Journal • P1 data • Hematological Disorders • Transplantation

PLX-R18 (Avoplacel), a Placental Expanded Mesenchymal-like Stromal Cell Therapy Shows Favorable Safety and Appears to Improve Incomplete Hematopoietic Recovery after Hematopoietic Cell Transplantation (HCT) (ASH 2022) - P1 | "PLX-R18 therapy appears to be safe and well tolerated and shows promise in improving incomplete hematopoietic recovery after HCT. Further clinical studies are warranted to optimize the efficacy of PLX-R18 in treatment of cytopenia in the post-HCT setting and expand the potential to other marrow failure disorders as well as cytopenia associated with certain treatment modalities such as CAR-T therapy."

Clinical • IO biomarker • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease • Febrile Neutropenia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelofibrosis • Neutropenia • Oncology • Pain • Septic Shock • Transplantation • CRP • CSF2 • IL6

[VIRTUAL] Safety and Demonstrated Efficacy of Placenta-Derived Cell Therapy PLX-R18 in Subjects with Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation: A Phase I International Multi-Center Study (ASH 2020) - P1 | "Upon completion, a large phase II trial, using the optimal dose, is considered for the same indication. Other attractive clinical areas for PLX-R18 therapy include acute radiation syndrome, bone marrow failure, aplastic anemia, myelofibrosis and with HCT as a “pan” cytokine to enhance rapid count recovery in all cells lines."

Clinical • P1 data • Aplastic Anemia • Graft versus Host Disease • Hematological Disorders • Immunology • Myelofibrosis • Oncology • Transplantation • CXCL8 • IL6

Prospective, Multi-Center, Phase I Clinical Trial of PLX-R18 Placental Expanded Adherent Stromal Cells in Subjects with Incomplete Hematopoietic Recovery after Hematopoietic Cell Transplantation (ASH 2018) - P1; "Upon completion, a larger phase II trial will be considered in the same indication using the optimal dose. Other potential uses include PLX-R18 therapy in Acute Radiation Syndrome, Bone marrow failure, and in HCT as a "pan" cytokine for rapid count recovery."

Clinical • P1 data • Biosimilar • CNS Disorders • Graft versus Host Disease • Immune Modulation • Immunology • Inflammation • Migraine • Pain • Transplantation

Pre-Administration of PLX-R18 Cells Protects Mice from Radiation-Induced Hematopoietic Failure and Lethality. (PubMed, Genes (Basel)) - "PLX-R18 administration attenuated biomarkers of bone marrow aplasia (EPO, FLT3L), sepsis (SAA), and systemic inflammation (sP-selectin and E-selectin) and attenuated radiation-induced inflammatory cytokines/chemokines and growth factors, including G-CSF, MIP-1a, MIP-1b, IL-2, IL-6 and MCP-1, In addition, PLX-R18 also ameliorated radiation-induced upregulation of pAKT. Taken together, prophylactic PLX-R18 administration may serve as a protection measure, mitigating bone marrow failure symptoms and systemic inflammation in the H-ARS model."

Biomarker • Journal • Preclinical • Aplastic Anemia • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Septic Shock • CCL3 • IL2 • IL6

Safety Evaluation of Intramuscular Injections of PLX-R18 in Subjects With Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation (clinicaltrials.gov) - P1; N=21; Completed; Sponsor: Pluristem Ltd.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Transplantation

Pluristem to Present Initial Results from Its Phase I HCT Study with PLX-R18 Demonstrating Safety and Efficacy at the ASH Annual Meeting (GlobeNewswire) - P1, N=21; "Pluristem Therapeutics...today reported the first clinical results for PLX-R18 in humans from its Phase I study evaluating PLX-R18 as a treatment for incomplete hematopoietic recovery following hematopoietic cell transplantation (HCT)....PLX-R18 demonstrated significant clinical improvements in Hb, ANC, and PLT among the high-dose cohort...PLX-R18 was found to be safe and well-tolerated...Topline results from the full Phase I clinical trial expected in Q1 2021 (n=21)..."

P1 data • Graft versus Host Disease • Immunology

Pluristem reports positive topline Phase I results in innovative hematology program, which is first to study PLX-R18 in humans (GlobeNewswire) - P1; N=21; NCT03002519; Sponsor: Pluristem Ltd.; "Pluristem Therapeutics Inc....today reported positive topline results in its first study to evaluate the safety and exploratory efficacy of PLX-R18 in humans. The company’s Phase I, open-label, dose-escalation study is evaluating the safety and exploratory efficacy of intramuscular injections of PLX-R18 in subjects with incomplete hematopoietic recovery following Hematopoietic Cell Transplantation (HCT)....The study enrolled 21 patients in the U.S. and Israel...The results demonstrate that PLX-R18 has the potential to stimulate the implanted hematopoietic cells to realize their therapeutic potential and generate improved blood counts over the long term in all three blood cell lineages at once...PLX-R18 was well-tolerated with a favorable safety profile."

P1 data • Graft versus Host Disease • Immunology

Safety Evaluation of Intramuscular Injections of PLX-R18 in Subjects With Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation (clinicaltrials.gov) - P1; N=21; Active, not recruiting; Sponsor: Pluristem Ltd.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Transplantation

Use of MSCs and MSC-educated macrophages to mitigate hematopoietic acute radiation syndrome. (PubMed, Curr Stem Cell Rep) - "We also discuss the first placental-derived MSC product to enter phase I trials, PLX-R18, and the challenges faced by bringing MSC and other cell therapies into the clinic for treating ARS. Although MSCs, MEMs and EEMs are potential cell therapy candidates in promoting hematopoietic HRS, challenges persist in translational clinical development of these products to the clinic. Whether any of these cellular therapies will be sufficient as stand-alone therapies to mitigate H-ARS or if they will be a bridging therapy that insures survival until a curative allogeneic hematopoietic stem cell transplant can be performed are the key questions that will have to be answered."

Journal • Hematological Disorders • Immunology • Inflammation • Transplantation

Pluristem Announces End of Patient Enrollment in its Phase I Hematology Study (GlobeNewswire) - "Pluristem Therapeutics...announced today it has completed patient enrollment in its Phase I study evaluating PLX-R18 as a treatment for incomplete hematopoietic recovery following hematopoietic cell transplantation (HCT), in the U.S. and in Israel....Pluristem expects to announce top line efficacy results during the first quarter of calendar year 2021."

Enrollment closed • P1 data • Graft versus Host Disease • Immunology

Safety Evaluation of Intramuscular Injections of PLX-R18 in Subjects With Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Pluristem Ltd.; Trial completion date: Jun 2020 ➔ Aug 2021; Trial primary completion date: Jun 2020 ➔ Aug 2021

Clinical • Trial completion date • Trial primary completion date • Transplantation

Open-label Phase I Study for PEP or Treatment of HS-ARS PLX-R18 for the Post-Exposure Prevention (PEP) or Treatment of Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS) (clinicaltrials.gov) - P1; N=27; Not yet recruiting; Sponsor: Pluristem Ltd.; Trial completion date: Dec 2019 ➔ Dec 2021; Trial primary completion date: Dec 2019 ➔ Dec 2021

Trial completion date • Trial primary completion date

"U.S. Department of Defense to Conduct Studies of #Pluristems #PLXR18 in a New ARS Project https://t.co/Y7A7uX5bH9 @RareDiseases" (@CheckOrphan)

Biosimilar

Pluristem Therapeutics announces FDA Orphan Drug Designation for PLX cell therapy for the treatment of graft failure and incomplete recovery following hematopoietic cell transplantation (GlobeNewswire) - "Pluristem Therapeutics...today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to the Company’s PLX cell therapy for the treatment of graft failure and incomplete hematopoietic recovery following hematopoietic cell transplantation...PLX-R18 is currently being evaluated for the treatment of insufficient hematopoietic recovery following bone marrow transplantation in an ongoing Phase 1 clinical trial in the U.S. and Israel."

Orphan drug • Graft versus Host Disease • Immunology

Mesenchymal Stromal Cells from Fetal and Maternal Placenta Possess Key Similarities and Differences: Potential Implications for Their Applications in Regenerative Medicine. (PubMed, Cells) - "We used cells developed by Pluristem LTD: PLacenta expanded mesenchymal-like adherent stromal cells (PLX), maternal-derived cells (PLX-PAD), fetal-derived cells (PLX-R18), and amniotic membrane-derived MSC (hAMSC). We show that MSCs and MSC-like cells from both fetal and maternal sources present immune modulatory properties versus lymphoid (T cells) and myeloid (APC) cells, whereby fetal-derived cells (PLX-R18 and hAMSC) have a stronger capacity to modulate immune cell proliferation and differentiation. Our results emphasize the importance of understanding the cell origin and characteristics in order to obtain a desired result, such as modulation of the inflammatory response that is critical in fostering regenerative processes."

Journal

Rescue from lethal acute radiation syndrome (ARS) with severe weight loss by secretome of intramuscularly injected human placental stromal cells. (PubMed, J Cachexia Sarcopenia Muscle) - "A well-regulated and orchestrated secretion of major pro-regenerative BM supporting secretome in high dose irradiated mice, treated with xenogeneic IM injected PLX-RAD cells, can explain the observed mitigation of ARS. This seemed to coincide with faster haematopoiesis regeneration, regain of severe weight loss and the increased survival rate. The ARS-related stress signals activating the IM injected PLX-RAD cells for the remote secretion of the relevant human proteins deserve further investigation."

Journal

Safety Evaluation of Intramuscular Injections of PLX-R18 in Subjects With Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Pluristem Ltd.; Trial completion date: May 2019 ➔ Jun 2020; Trial primary completion date: May 2019 ➔ Jun 2020

Clinical • Trial completion date • Trial primary completion date

"$PSTI Announces Completion of 2nd Cohort and DSMB Approval to Enroll Final Cohort in Phase I Hematological Study of PLX-R18" (@BioStocks)

DSMB • P1 data