COVID-19 infection therapeutic - Charite University of Medicine Berlin/Pluri
Latest Information Update: 13 Mar 2023
At a glance
- Originator Charite - Universitatsmedizin Berlin; Pluristem Therapeutics
- Developer Pluri
- Class Anti-inflammatories; Antivirals; Stem cell therapies
- Mechanism of Action Cell replacements; Immunomodulators
-
Orphan Drug Status
No
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity No
Highest Development Phases
- Clinical Phase Unknown COVID 2019 infections
Most Recent Events
- 08 Jul 2021 Pluristem Therapeutics withdraw collaborative research agreement with Innovare R&D for a phase II trial for SARS-COV-2 acute respiratory disease in Mexico
- 29 Dec 2020 Pluristem Therapeutics enters into collaborative research agreement with Innovare R&D for phase II trial of PLX cell product candidates for SARS-COV-2 acute respiratory disease in Mexico
- 21 Jul 2020 Pluristem Therapeutics plans a phase II trial for COVID-2019 in Germany
Development Overview
Introduction
A COVID-19 infection therapeutic is being developed by Pluri (formerly Pluristem Therapeutics) in collaboration with BIH Center for Regenerative Therapy (BCRT) and the Berlin Center for Advanced Therapies (BeCAT) at the Charite’ University of Medicine Berlin, for the treatment of respiratory and inflammatory complications associated with the COVID-19 coronavirus, utilising Pluristem's patent-protected PLacental expanded (PLX) cellular drug candidates. The collaboration aims to treat severe pneumonia resulting from COVID-19 and preventing the deterioration of patients with SARS-COV-2 acute respiratory disease and sepsis. The PLX cells are available for per patient compassionate use in Israel. Clinical development is underway in USA, Israel and Mexico and early research is underway in Germany.
PLX cells are placenta-derived, allogeneic mesenchymal-like adherent stromal cells possessing immunomodulatory properties that invoke the immune system’s natural regulatory T cells and M2 macrophages, thus precluding or reversing the accidental over-activation of the immune system. These attributable characteristics of the cells are expected to potentially reduce the fatal symptoms of COVID-19 induced pneumonia and pneumonitis. The cells release soluble biomolecules, inclusive of cytokines, chemokines and growth factors, which act in a paracrine or endocrine manner, to heal damaged tissue by stimulating the body’s own regenerative mechanisms. The PLX cells are grown utilising the company's proprietary three-dimensional expansion technology, and are amenable to patient administration off-the-shelf, without the need for tissue matching.
In November 2007, Pluristem Life Systems was renamed as Pluristem Therapeutics [1] .
In July 2022, Pluristem Therapeutics changed its name to Pluri [2] .
Company Agreements
In July 2021, Pluristem Therapeutics (now Pluri) announced that, the company will not pursue plans announced in December 2020 to expand Pluristem’s COVID-19 program to Mexico in collaboration with Innovare R&D in response to COVID-19’s evolution as a disease, as well as changes in the standard of care and a decline in the most severe cases.
In December 2020, Pluristem Therapeutics entered into a collaboration agreement with Mexican pharmaceutical company Innovare R&D to expand its ongoing phase II clinical programme of PLX cells product candidates in the treatment of acute respiratory distress syndrome (ARDS) associated with COVID-2019 infections in Mexico. Under the terms of the agreement, Innovare will open clinical sites and enrol patients for the proposed clinical study in Mexico. Innovare will fund the study in Mexico and will purchase PLX cells for the trial from Pluristem. Subject to potential positive clinical study results and Mexican regulatory approval for commercialization, the agreement grants Innovare exclusive distribution rights in Mexico to supply PLX cells for treating severe COVID-19 cases complicated by ARDS. All intellectual property and manufacturing rights remain with Pluristem. [3] [2]
In March 2020, Pluristem Therapeutics (now Pluri) expanded its existing framework and research agreement with Charite’ University of Medicine Berlin, to conduct a joint, collaborative project, to assess the therapeutic effects of Pluristem’s patented PLX cell product candidates, for potential treatment of the respiratory and inflammatory complications related to the COVID-19 coronavirus. Specifically, the collaboration will involve the BIH Center for Regenerative Therapy (BCRT) and the Berlin Center for Advanced Therapies (BeCAT) at Charite’ University of Medicine Berlin. Earlier, in October 2015, the company had expanded its five-year collaborative research agreement with the University of Medicine, Berlin. The companies completed orthopedic phase I/II study and have also collaborated on other indications including kidney disease, cardiovascular indications and comprehensive immunological research for Pluristem’s Peripheral Artery Disease clinical programs. Earlier, in August 2012, Pluristem Therapeutics Inc. renewed the five-year collaborative research agreement with the University of Medicine Berlin. BCRT and Pluristem were to collaborate on Pluristem's phase I/II clinical trial in Germany on the regeneration of injured gluteal muscle, as well as on immunological research and the development of new product candidates. The agreement between Pluristem Life Systems and Berlin-Brandenburg Center for Regenerative Therapy (BCRT) at Charité - University Medicine Berlin was originally entered into, in July 2007. Pluristem and BCRT were to collaborate on a variety of indications utilizing mesenchymal stem cells derived from the placenta that have been expanded in the Company's proprietary PluriX™ 3-D bioreactor. The initial focus of the collaboration wsa on neurological indications such as Multiple Sclerosis and Parkinson's disease. The agreement also covered organ transplantation and cardiovascular indications such as inflammatory cardiomyopathy. Pluristem is the exclusive owner of the technology and any products stemming from the collaboration. [4] [5] [6] [7] [2]
Key Development Milestones
In July 2021, Pluristem Therapeutics announced that, the company will not pursue expansion of COVID-19 program to Mexico in collaboration with Innovare R&D, announced in December 2020, due to COVID-19’s evolution as a disease, as well as changes in the standard of care and a decline in the most severe cases. Prior to December 2020, Pluristem Therapeutics plans to initiate a phase II trial of PLX cell therapy in the treatment of SARS-COV-2 acute respiratory disease in Mexico. The phase II trial in Mexico is subject to the approval of local authorities, Mexico Ministry of Health, with the goal of being conducted under the US FDA cleared protocol [8] [3] .
In April 2020, Pluristem Therapeutics announced the treatment of first patient with COVID-2019 infection with PLX cell therapy in the US under the US FDA's compassionate use programme. The single patient expanded access programme is a part of the US Coronavirus Treatment Acceleration Program (CTAP). In March 2020, Pluristem announced its intention to initiate development in the US [9] [10] [11] .
As of March 2020, Pluristem Therapeutics announced that three patients have been treated under a per-patient compassionate use program for the treatment of COVID-19 infections in Israel. The company also expects to enrol other patients in Israel. Earlier, in March 2020, the Israeli Ministry of Health approved Pluristem’s request to seek approval for PLX cell product candidates to treat COVID-19 coronavirus patients under the per-patient compassionate use framework in Israel. In April 2020, preliminary efficacy data form this program was released by Pluristem. In May 2020, a 28 day follow up data were released by Pluristem [12] [13] [14] [15] [16] .
Financing Information
In May 2020, Pluristem Therapeutics entered into a definitive agreements with two institutional investors for offering of common stocks. Net proceeds of approximately $US15 million will be used for working capital, including funding for phase II trial of PLX cell therapy in the treatment of complications secondary from COVID-2019 infections and other clinical trial activities, investment in capital equipment and other general corporate purposes [17] .
In May 2021, Pluristem Therapeutics announced the receipt of a “Disbursement Offer” of approximately $US 24 million from the European Investment Bank (EIB). This disbursement – first in three tranches of funding – indicates that the company achieved a key milestone of the previously announced non-dilutive financing agreement. As per the EIB agreement, Pluristem expects to receive the first tranche of funds during June 2021. Pluristem intends to use this funding for operational, clinical, and R&D activities to advance its regenerative medicine platform [18] . Earlier in April 2020, Pluristem Therapeutics announced the approval of approximately $US 60.9 million non-dilutive financing from the European Investment Bank (EIB). The finance will be used for Pluristem’s research and development in the EU to further advance its regenerative cell therapy platform, to assist moving the products in its pipeline to market and clinical development of PLX cells as a treatment for complications associated with COVID-19. The expected signing date of the financing agreement relating to the Approved Financing was April 30, 2020 [19]
Patent Information
Pluristem Therapeutics has a large portfolio of issued patents and pending patent applications spanning 30 active patent families and 52 countries, including over 115 issued patents. The portfolio extenstively covers Pluristem’s cells and pharmaceutical compositions containing them, therapeutic uses (second medical uses) thereof, manufacturing methods and devices involved in the expansion and harvesting of adherent stromal cells, along with their subsequent controlled thawing after cryopreservation (Pluristem Therapeutics website, March 2020).
Drug Properties & Chemical Synopsis
- Route of administration Parenteral
- Formulation unspecified
- Class Anti-inflammatories, Antivirals, Stem cell therapies
- Target Cell
- Mechanism of Action Cell replacements; Immunomodulators
-
WHO ATC code
V03A-X (Other therapeutic products)
-
EPhMRA code
V3X (All Other Therapeutic Products)
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| COVID 2019 infections | compassionate use programme | - | Clinical Phase Unknown | Israel, USA | Parenteral / unspecified | Pluri | 13 Apr 2020 |
| COVID 2019 infections | - | - | Research | Germany | Parenteral / unspecified | Pluri | 12 May 2020 |
Priority Development Status
| Type | Region | Indication |
|---|---|---|
| Coronavirus Treatment Acceleration Program | USA | COVID 2019 infections |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Pluristem Therapeutics | Originator | Israel |
| Charite - Universitatsmedizin Berlin | Originator | Germany |
| Pluri | Owner | Israel |
| European Investment Bank | Funder | Luxembourg |
Scientific Summary
Therapeutic Trials
Preliminary data from PLX cell against COVID-19 infections reported 87.5% survival rate in eight patients in the 28 day follow up. Improvement in respiratory parameters was observed in 4 out of 6 patients and 75% patients survived without assistance of ventilators. In addition, 62.5% patients were discharged alive from the hospital in comparison to 3.3% patients requiring mechanical ventilation. One patient has shown no change in respiratory parameters, is still breathing with the assistance of a ventilator and remains relatively stable. Deterioration in respiratory parameters was observed in one patient. Two patients out of four with multi-organ failure prior to treatment, showed clinical recovery in addition to the respiratory improvement [12] [13] [16]
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 26 Jul 2022 | Company Involvement | Pluristem Therapeutics is now called Pluri Updated 13 Mar 2023 |
| 08 Jul 2021 | Licensing Status | Pluristem Therapeutics withdraw collaborative research agreement with Innovare R&D for a phase II trial for SARS-COV-2 acute respiratory disease in Mexico [8] Updated 13 Jul 2021 |
| 29 Dec 2020 | Licensing Status | Pluristem Therapeutics enters into collaborative research agreement with Innovare R&D for phase II trial of PLX cell product candidates for SARS-COV-2 acute respiratory disease in Mexico [3] Updated 31 Dec 2020 |
| 29 Dec 2020 | Trial Update | Pluristem Therapeutics plans a phase II trial for SARS-COV-2 acute respiratory disease in Mexico [3] Updated 31 Dec 2020 |
| 21 Jul 2020 | Trial Update | Pluristem Therapeutics plans a phase II trial for COVID-2019 in Germany Updated 24 Jul 2020 |
| 14 May 2020 | Scientific Update | Efficacy data from a COVID-19 compassionate use program released by Pluristem Therapeutics [12] Updated 19 May 2020 |
| 13 Apr 2020 | Regulatory Status | The US FDA clears the Pluristem Therapeutics' placental expanded (PLX) cell therapy for COVID-2019 infections in USA under Coronavirus Treatment Acceleration Program [9] Updated 04 Jan 2021 |
| 13 Apr 2020 | Phase Change - Clinical | Clinical trials in COVID-2019 infections in USA (Parenteral) - compassionate use programme [9] Updated 16 Apr 2020 |
| 07 Apr 2020 | Scientific Update | Efficacy data from a COVID-19 Compassionate Use Program released by Pluristem [13] Updated 15 Apr 2020 |
| 26 Mar 2020 | Trial Update | Pluristem plans a phase II study in COVID-2019 infections in USA (Parenteral) in 2020 [10] [12] Updated 01 Apr 2020 |
| 18 Mar 2020 | Patent Information | Pluristem Therapeutics has patent protection for its PLX cells and associated technologies (Pluristem Therapeutics website, March 2020) Updated 18 Mar 2020 |
| 18 Mar 2020 | Patent Information | Pluristem Therapeutics has patents pending for its PLX cells and associated technology (Pluristem Therapeutics website, March 2020) Updated 18 Mar 2020 |
| 17 Mar 2020 | Phase Change - Clinical | Clinical trials in COVID-2019 infections in Israel (Parenteral) - compassionate use programme [14] Updated 19 Mar 2020 |
| 17 Mar 2020 | Regulatory Status | The Israeli Ministry of Health approves per patient compassionate use of PLX cell product candidates for COVID-2019 infections in Israel [14] Updated 19 Mar 2020 |
| 12 Mar 2020 | Licensing Status | Pluristem Therapeutics expands its collaborative research agreement with Charite University of Medicine Berlin for respiratory and inflammatory complications associated with the COVID-19 coronavirus [7] Updated 18 Mar 2020 |
| 12 Mar 2020 | Phase Change | Early research in COVID-2019 infections in Germany (Parenteral) [7] Updated 18 Mar 2020 |
| 12 Mar 2020 | Phase Change | Early research in COVID-2019 infections in Israel (Parenteral) [7] Updated 18 Mar 2020 |
| 10 Jul 2007 | Licensing Status | Pluristem Therapeutics signs a collaborative research agreement with Charite University of Medicine Berlin for multiple indications utilizing Pluristem's placental mesenchymal stem cells (MSCs) [4] Updated 18 Mar 2020 |
References
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Pluristem's Reverse Stock Split Effective Today.
Media Release -
Pluristem Therapeutics Inc. Changes its Name to ##8220##Pluri Inc.##8221## Reflecting the Company's Strategy to Leverage its Innovative 3D Cell-based Technology Platform to Additional Industries.
Media Release -
Pluristem Enters Collaboration With Pharmaceutical Company Innovare R&D to Expand Pluristems ARDS Associated With COVID-19 Program to Mexico.
Media Release -
Pluristem and Center for Regenerative Therapies at Charite University Hospital of Berlin Enters into Collaborative Research Agreement.
Media Release -
Pluristem and World Renowned Charite Berlin-Brandenburg Center for Regenerative Therapies Renew Five-Year Collaborative Research Agreement.
Media Release -
Pluristem & Charite Expand Cooperation Agreement to Include Orthopedic Indications.
Media Release -
Pluristem and Charit University of Medicine Berlin Join Forces Targeting Potential Treatment for Respiratory and Inflammatory Intratissue Complications Caused by COVID-19.
Media Release -
Pluristem Brings ARDS Associated with COVID-19 Phase II Studies to Clinical Readout.
Media Release -
Pluristem Expands its Compassionate Use Program: Treated First COVID-19 Patient in U.S. Under FDA Single Patient Expanded Access Program.
Media Release -
Pluristem Provides Update on COVID-19: Preparedness, Current Phase III Clinical Trials Status and Treatment Development Activity.
Media Release -
Expanded Access Program for the potential use of PLX cells in the treatment of Single Patient suffering from complications associated with COVID-19
ctiprofile -
Pluristem Provides 28-Day Follow Up for Ventilator-Dependent COVID-19 Patients under Compassionate Use Program in Israel and U.S.
Media Release -
Pluristem Reports Preliminary Data from its COVID-19 Compassionate Use Program, Treating Seven Patients with Acute Respiratory Failure.
Media Release -
Israeli Ministry of Health Clears a Path to Allow Per Patient Compassionate Use Treatment of Covid-19 Patients with Pluristems PLX Cells.
Media Release -
Pluristem Treated First Three COVID-19 Patients in Israel under Compassionate Use.
Media Release -
A trial conducted under a compassionate program for COVID-19 patients
ctiprofile -
Pluristem Announces Pricing of Its Registered Direct Offering for Aggregate Proceeds of $15 Million.
Media Release -
Pluristem to Receive 20M Non-Dilutive Funding from the European Investment Bank.
Media Release -
Pluristem Secures 50 Million Non-Dilutive Financing from the European Investment Bank to Support its COVID-19 Project and Phase III Studies.
Media Release
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