This study is a single center trial to assess the safety and initial efficacy of intra-articular administration of Allocetra to patients with Temporomandibular Joint Osteoarthritis (TMJ-OA)

Start Date15 Dec 2024

Sponsor / Collaborator

Sheba Medical Center

[+1]

NCT06522035

/ RecruitingPhase 1

Evaluation of Allocetra by Intra-articular Injection for the Treatment of Psoriatic Arthritis

This is an open label study to evaluate the safety and initial efficacy of intra-articular administration of Allocetra in patients with Psoriatic Arthritis (PsA).

Start Date01 Aug 2024

Sponsor / Collaborator

Enlivex Therapeutics Ltd.

CTIS2023-508748-23-00

/ Not yet recruitingPhase 1/2

A Phase 1/2a Randomized, Double-Blind Placebo-controlled Study of Intra-articular Allocetra in Knee Osteoarthritis - ENX-CL-05-001

Start Date16 Apr 2024

Sponsor / Collaborator

Enlivex Therapeutics Ltd.

100 Clinical Results associated with Leukocyte cell therapy (Enlivex Therapeutics)

100 Translational Medicine associated with Leukocyte cell therapy (Enlivex Therapeutics)

100 Patents (Medical) associated with Leukocyte cell therapy (Enlivex Therapeutics)

Literatures (Medical) associated with Leukocyte cell therapy (Enlivex Therapeutics)

19 Aug 2024·MILITARY MEDICINE

Apoptotic Cell–Based Therapy for the Modification of the Inflammatory Response to Hemorrhagic Shock

Article

Author: Lutsker, Maya ; Kolben, Yotam ; Mevorach, Dror ; Aliev, Emil ; Wagnert-Avraham, Linn ; Kenig, Ariel ; Kessler, Asa ; Nachman, Dean

ABSTRACT:

Introduction:

Many trauma patients die from hemorrhagic shock in the military and civilian settings. Although two-thirds of hemorrhagic shock victims die of reasons other than exsanguination, such as the consequent cytokine storm, anti-inflammatory therapies failed to be utilized. Apoptotic cell–based treatments enhance innate ability to exert systemic immunomodulation as demonstrated in several clinical applications and hence might present a novel approach in hemorrhagic shock treatment.

Materials and Methods:

Twenty-two rats underwent a pressure-controlled hemorrhagic shock model and followed up for 24 hours. An infusion of apoptotic cells (Allocetra-OTS, Enlivex Therapeutics Ltd, Nes Ziona, Israel) was administered to the treatment group. Hemodynamics, blood counts, biochemistry findings, and cytokine profile were compared to a saline-resuscitated control group.

Results:

The treatment group’s mean arterial pressure decreased from 94.8 mmHg to 28.2 mmHg, resulting in an 8.13 mg/dL increase in lactate and a 1.9 g/L decrease in hemoglobin, similar to the control group. White blood cells and platelets decreased more profoundly in the treatment group. A similar cytokine profile after 24 hours was markedly attenuated in the treatment group 2 hours after bleeding. Levels of pro-inflammatory cytokines such as interleukin (IL)-1a (28.4 pg/mL vs. 179.1 pg/mL), IL-1b (47.4 pg/mL vs. 103.9 pg/mL), IL-6 (526.2 pg/mL vs. 3492 pg/mL), interferon γ (11.4 pg/mL vs. 427.9 pg/mL), and tumor necrosis factor α (19.0 pg/mL vs. 31.7 pg/mL) were profoundly lower in the treatment group.

Conclusion:

In a pressure-control hemorrhagic shock model in rats, apoptotic cell infusion showed preliminary signs of a uniform attenuated cytokine response. Apoptotic cell–based therapies might serve as a novel immunomodulatory therapy for hemorrhagic shock.

13 Apr 2023·Journal of hematology & oncology

Cancer and COVID-19: unravelling the immunological interplay with a review of promising therapies against severe SARS-CoV-2 for cancer patients.

Review

Author: Park, Chandler H. ; Joshi, Muskan ; Menon, Gayathri P. ; Sharma, Pushpa ; Cappelli, Jared ; Emmanuel, Nancy ; Wilkerson, William B. ; Leyfman, Yan ; Erick, Timothy K.

Cancer patients, due to their immunocompromised status, are at an increased risk for severe SARS-CoV-2 infection. Since severe SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation while stimulating hypoxia, and malignancy promotes hypoxia-induced cellular metabolic alterations leading to cell death, we propose a mechanistic interplay between both conditions that results in an upregulation of IL-6 secretion resulting in enhanced cytokine production and systemic injury. Hypoxia mediated by both conditions results in cell necrosis, dysregulation of oxidative phosphorylation, and mitochondrial dysfunction. This produces free radicals and cytokines that result in systemic inflammatory injury. Hypoxia also catalyzes the breakdown of COX-1 and 2 resulting in bronchoconstriction and pulmonary edema, which further exacerbates tissue hypoxia. Given this disease model, therapeutic options are currently being studied against severe SARS-COV-2. In this study, we review several promising therapies against severe disease supported by clinical trial evidence-including Allocetra, monoclonal antibodies (Tixagevimab-Cilgavimab), peginterferon lambda, Baricitinib, Remdesivir, Sarilumab, Tocilizumab, Anakinra, Bevacizumab, exosomes, and mesenchymal stem cells. Due to the virus's rapid adaptive evolution and diverse symptomatic manifestation, the use of combination therapies offers a promising approach to decrease systemic injury. By investing in such targeted interventions, cases of severe SARS-CoV-2 should decrease along with its associated long-term sequelae and thereby allow cancer patients to resume their treatments.

01 Jan 2023·Frontiers in immunology

Apoptotic cells for treatment of acute respiratory distress syndrome associated with COVID-19.

Article

Author: Abutbul, Avraham ; Reicher, Barak ; Makram, Nassar ; Binder, Lior ; van Heerden, Peter Vernon ; Nachshon, Akiva ; Naama, Ahmad ; Maayan, Shlomo ; Mevorach, Dror ; Abu Jabal, Kamal ; Shabat, Yehudit ; Hershkovitz, Oren

Background:

Hyper-inflammatory immune response, a hallmark of severe COVID-19, is associated with increased mortality. Acute respiratory distress syndrome (ARDS) is a common manifestation. We undertook two phase I/II studies in five and then 16 subjects with severe/critical COVID-19 to assess the safety and preliminary efficacy of apoptotic cells (Allocetra™-OTS, Enlivex Therapeutics), a cellular immunomodulatory therapy that reprograms macrophages to reduce hyper-inflammatory response severity.

Methods:

Eligible patients presenting to the Emergency Room with severe COVID-19 and respiratory dysfunction received one intravenous administration of Allocetra™-OTS and were monitored for adverse events (AEs) for 28 days. The primary aim was to determine the safety profile of treatment; secondary aims were recovery from ARDS, intensive care unit (ICU) and hospital length-of-stay, and mortality. Immune modulator markers were measured to elucidate the mechanism of action of Allocetra™-OTS.

Results:

21 patients with severe-critical COVID-19 of Gamma, Alpha and Delta variants, were treated with a single dose of apoptotic cells. 19/21 patients had mild-to-severe ARDS at presentation. Median age was 53 years, 16/21 were males, 16/21 were overweight/obese. No serious related adverse events (SAEs) were reported. All 21 study subjects survived to day 28 (end of study); 19/21 recovered completely. Comparable mortality rates at the hospital were 3.8%-8.9% for age- and gender-matched patients, and 39%-55% for critical patients. Recovering patients exhibited rapid ARDS resolution and parallel resolution of inflammation markers and elevated cytokines/chemokines.

Conclusion:

In patients with severe/critical COVID-19 associated with ARDS, Allocetra™-OTS was safe, well-tolerated, and showed promising results for resolution of respiratory failure and inflammation.

Trial registration:

https://clinicaltrials.gov/ct2/show/study/NCT04513470, https://clinicaltrials.gov/ct2/show/study/NCT04590053, Identifiers NCT04513470, NCT04590053.

News (Medical) associated with Leukocyte cell therapy (Enlivex Therapeutics)

23 Apr 2025

·www.globenewswire.com

Enlivex Therapeutics to Showcase Allocetra’s Potential in Osteoarthritis at OARSI 2025 World Congress

Presentations to underscore AllocetraTM’s novel mechanism targeting immune imbalance in joint disease Ness-Ziona, Israel, April 23, 2025 (GLOBE NEWSWIRE) -- Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the “Company”), a clinical-stage macrophage reprogramming immunotherapy company, today announced that it will present two poster abstracts at the Osteoarthritis Research Society International (OARSI) 2025 World Congress on Osteoarthritis, taking place April 24-27, 2025, in Incheon (Seoul), South Korea. “These presentations at OARSI 2025 will highlight the growing body of evidence supporting Allocetra’sTM potential as a novel therapeutic approach for osteoarthritis,” said Oren Hershkovitz, PhD, Chief Executive Officer of Enlivex. “We believe that restoring macrophage homeostasis may address the underlying drivers of chronic joint inflammation and cartilage degradation, potentially offering a promising new treatment pathway for millions of patients worldwide.” The presentations will feature data from both preclinical and clinical studies evaluating Allocetra™, Enlivex’s proprietary, off-the-shelf macrophage reprogramming cell therapy, in patients with osteoarthritis. Allocetra™ is designed to reprogram macrophages into a homeostatic state, thereby promoting immune balance and resolving chronic inflammation. Allocetra™ has demonstrated favorable safety and promising efficacy signals in Phase I/II studies in moderate and end-stage osteoarthritis, including substantial and durable pain reduction, improved joint function, and avoidance of knee replacement surgery. Preclinical studies have further supported its unique mechanism of action in modulating macrophage-driven inflammation. Accepted Presentations: Flash Talk & Poster Presentation Title: Phase I/II Clinical Trial of Allocetra™ Cell Therapy for Knee Osteoarthritis: Initial Evidence of Response to Inflammation ModulationAbstract Publication Number: 092Flash Talk Session: Pain Mechanisms and Neuroinflammation in OADate & Time: April 26, 2025 | 11:31 – 11:33 AM KSTPoster Sessions: Friday, April 25 | 4:15 – 5:00 PM KSTSaturday, April 26 | 4:15 – 5:00 PM KST Poster Number: 092 Poster Presentation Title: Biological Activity Characterization of Allocetra™, a Novel Macrophage Reprogramming Cell Therapy, in Osteoarthritis Preclinical ModelsAbstract Control ID: 4231304Poster Sessions: Friday, April 25 | 3:30 – 4:15 PM KSTSaturday, April 26 | 3:30 – 4:15 PM KST Poster Number: 665 Dr. Oren Hershkovitz, CEO and Einat Galamidi, MD, CMO, will attend the conference and be available for meetings with stakeholders and members of the scientific community. ABOUT ENLIVEX Enlivex is a clinical stage macrophage reprogramming immunotherapy company developing Allocetra™, a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Resetting non-homeostatic macrophages into their homeostatic state is critical for immune system rebalancing and resolution of life-threatening and life debilitating conditions. For more information, visit http://www.enlivex.com. Safe Harbor Statement: This press release contains forward-looking statements, which may be identified by words such as “expects,” “plans,” “projects,” “will,” “may,” “anticipates,” “believes,” “should,” “would”, “could,” “intends,” “estimates,” “suggests,” “has the potential to” and other words of similar meaning, including statements regarding expected cash balances, market opportunities for the results of current clinical studies and preclinical experiments, the effectiveness of, and market opportunities for, ALLOCETRA TM programs. All such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that forward-looking statements involve risks and uncertainties that may affect Enlivex’s business and prospects, including the risks that Enlivex may not succeed in generating any revenues or developing any commercial products; that the products in development may fail, may not achieve the expected results or effectiveness and/or may not generate data that would support the approval or marketing of these products for the indications being studied or for other indications; that ongoing studies may not continue to show substantial or any activity; and other risks and uncertainties that may cause results to differ materially from those set forth in the forward-looking statements. The results of clinical trials in humans may produce results that differ significantly from the results of clinical and other trials in animals. The results of early-stage trials may differ significantly from the results of more developed, later-stage trials. The development of any products using the ALLOCETRA TM product line could also be affected by a number of other factors, including unexpected safety, efficacy or manufacturing issues, additional time requirements for data analyses and decision making, the impact of pharmaceutical industry regulation, the impact of competitive products and pricing and the impact of patents and other proprietary rights held by competitors and other third parties. In addition to the risk factors described above, investors should consider the economic, competitive, governmental, technological and other factors discussed in Enlivex’s filings with the Securities and Exchange Commission, including in the Company’s most recent Annual Report on Form 20-F filed with the Securities and Exchange Commission. The forward-looking statements contained in this press release speak only as of the date the statements were made, and we do not undertake any obligation to update forward-looking statements, except as required under applicable law. Contact:Dave Gentry, CEORedChip Companies, Inc.1-407-644-4256ENLV@redchip.com

Cell TherapyImmunotherapyClinical Study

23 Apr 2025

·www.globenewswire.com

Enlivex Announces Completion of Enrollment In The Phase II stage Of Its Phase I/II Trial Evaluating Allocetra In Patients With Moderate To Severe Knee Osteoarthritis

April 21, 2025 -- Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the “Company”), a clinical-stage macrophage reprogramming immunotherapy company, today announced that the Company completed enrollment of all patients in the Phase II stage of its randomized, controlled, blinded Phase I/II trial of Allocetra™ in patients with moderate to severe knee osteoarthritis. Overall, 133 patients were randomized and treated in the Phase II stage. Oren Hershkovitz, Ph.D, CEO of Enlivex, commented, “We are pleased to have completed the recruitment of patients in the Phase II stage of this trial, which follows the recently announced promising initial efficacy data from the Phase I stage. We therefore reiterate our timeline objective to obtain 3-month topline data by August 2025. We believe Allocetra™ has the potential to transform the way osteoarthritis patients are being treated today, and we are eager to receive the topline data of the trial.” The multi-center Phase I/II clinical trial consists of two stages. The first stage was a Phase I safety run-in, open-label dose escalation phase to characterize the safety and tolerability of Allocetra™ injections to the target knee, in order to identify the dose and injection regimen for the subsequent Phase II stage. Recently the Company announced positive interim 3-month and 6-month efficacy data for the first 12 patients treated in this Phase I stage, demonstrating marked statistically significant improvements in all key efficacy endpoints and no safety issues. The Phase II stage, which completed its patient enrollment, is a double-blind, randomized, placebo-controlled multi-center trial. In addition to evaluating safety, the study design includes an interim statistical evaluation, conducted by an independent third party and blinded to the Company, to assess the potential value of the enrollment of up to 50 patients in addition to the originally targeted randomized sample size, and its marginal impact on the p-value of the statistical estimation of the total group and/or specific sub-group. In addition, the study incorporates an independent data safety and monitoring board (DSMB) that reviews the safety data at predefined time points. The trial’s key efficacy end points will evaluate joint-pain and joint-function in comparison to placebo at three months, six months and post treatment, including 12 month follow up. The Company expects a topline data readout from the Phase II stage, including full 3-month endpoints, by August 2025 . Osteoarthritis is by far the most common form of arthritis, affecting more than 32.5 million Americans and more than 300 million individuals worldwide. About half of knees with ACL injuries develop osteoarthritis within 5 to 15 years. 78 million Americans are projected to have osteoarthritis by the year 2040. Symptomatic knee osteoarthritis is particularly prevalent and disabling, with 40% of men and 47% of women developing knee osteoarthritis in their lifetimes. Osteoarthritis accounts for over one million hospitalizations annually in the United States, primarily for total joint replacement. The burden of osteoarthritis is enormous, and the need for treatments that reduce pain and attendant disability for persons with osteoarthritis is critical. There are currently no medications approved by either the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA) that have been demonstrated to arrest, slow or reverse progression of structural damage in the joint. Enlivex is a clinical stage macrophage reprogramming immunotherapy company developing Allocetra™, a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Resetting non-homeostatic macrophages into their homeostatic state is critical for immune system rebalancing and resolution of life-threatening and life debilitating conditions. The content above comes from the network. if any infringement, please contact us to modify.

ImmunotherapyClinical ResultCell Therapy

04 Apr 2025

·pipelinereview.com

Enlivex Announces the Dosing of the First Patient in a Phase I Trial Evaluating Allocetra in Patients with TMJ Osteoarthritis

NESS-ZIONA, Israel I April 03, 2025 I Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the “Company” or “Enlivex”), a clinical-stage macrophage reprogramming immunotherapy company, today announced that the first patient has been dosed in an investigator-initiated Phase I trial to evaluate the safety, tolerability and initial efficacy of Allocetra™ for injection into the temporomandibular joint (TMJ) in patients suffering from TMJ osteoarthritis. The study will be conducted by the Rheumatology Unit at Sheba Medical Center in collaboration with the Department of Oral and Maxillofacial Surgery at Sheba Medical Center. Notably, Sheba Medical Center was recently ranked among the top 10 hospitals in the world by Newsweek . Dr. Einat Galamidi, CMO of Enlivex, commented, “This study will provide a preliminary evaluation of the safety and potential effect of Allocetra TM for the treatment of TMJ osteoarthritis, which affects a joint that is critical for daily function. We are pleased to report that the injection of Alloctera TM into the first patient’s TMJ was successfully completed with no complications.” The trial currently plans to recruit six patients who have insufficiently responded to conventional therapies for TMJ osteoarthritis. The trial’s primary safety endpoint will measure the frequency and severity of adverse events and serious adverse events, and efficacy endpoints will assess changes from baseline in TMJ pain, joint functionality, and other disease parameters for up to 12 months following administration of Allocetra™. ABOUT ALLOCETRA™ Allocetra™ is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra™ has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as “unmet medical needs,” as a stand-alone therapy or in combination with leading therapeutic agents. ABOUT TEMPOROMANDIBULAR JOINT (TMJ) OSTEOARTHRITIS TMJ disorders are the second most common musculoskeletal condition affecting five to 12% of the population globally, with an annual health cost estimated at $4 billion 1 . Osteoarthritis of the TMJ is the most common form of arthritis in the TMJ, causing pain and stiffness in the jaw. It may become difficult to chew. TMJ osteoarthritis is a degenerative disease of the joint, which culminates in the progressive destruction of all soft and hard tissue components of the TMJ. For patients who present in early adulthood with severe clinical symptoms and catastrophic radiographic changes, there are significant implications for management, including the potential need for early total joint replacement. There are currently no effective long-term treatments for this disease 2 . ABOUT ENLIVEX Enlivex is a clinical stage macrophage reprogramming immunotherapy company developing Allocetra™, a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Resetting non-homeostatic macrophages into their homeostatic state is critical for immune system rebalancing and resolution of life-threatening conditions. For more information, visit http://www.enlivex.com . 1 Bianchi et al., Sci Rep 2020 2 Delpachitra et al., British Journal of Oral and Maxillofacial Surgery 60 (2022) SOURCE: Enlivex

Cell TherapyImmunotherapyPhase 1

100 Deals associated with Leukocyte cell therapy (Enlivex Therapeutics)

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Indication	Highest Phase	Country/Location	Organization	Date
Osteoarthritis, Knee	Phase 2	United States	Enlivex Therapeutics Ltd.	26 Jan 2024
Osteoarthritis, Knee	Phase 2	Denmark	Enlivex Therapeutics Ltd.	26 Jan 2024
Osteoarthritis, Knee	Phase 2	Israel	Enlivex Therapeutics Ltd.	26 Jan 2024
Advanced Malignant Solid Neoplasm	Phase 2	Israel	Enlivex Therapeutics Ltd.	15 Nov 2022
Advanced Malignant Solid Neoplasm	Phase 2	Spain	Enlivex Therapeutics Ltd.	15 Nov 2022
Peritoneal Neoplasms	Phase 2	Israel	Enlivex Therapeutics Ltd.	15 Nov 2022
Peritoneal Neoplasms	Phase 2	Spain	Enlivex Therapeutics Ltd.	15 Nov 2022
Neoplasm Metastasis	Phase 2	Israel	Enlivex Therapeutics Ltd.	29 Jun 2022
Respiratory Distress Syndrome, Acute	Phase 2	Israel	Enlivex Therapeutics Ltd.	01 Sep 2021
Cholangitis	Phase 2	Belgium	Enlivex Therapeutics Ltd.	30 Nov 2020

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06233474 (GlobeNewswire) Manual	Phase 1/2	Osteoarthritis, Knee	12	Allocetra	reflctyizh(wdwnhiswuw) = hauosvokif ylqyojtpea (nmnnwbnezm ) View more	Positive	03 Dec 2024
NCT06233474 (Biospace) Manual	Phase 1/2	Osteoarthritis, Knee	9	Allocetra	eamspzjfag(zxsnqlompm) = etfvoowcsa xucehylifc (dpgwbgnlqf ) View more	Positive	17 Jun 2024
NCT04612413 (GlobeNewswire) Manual	Phase 2	Sepsis	-	Allocetra	cbstgwijuz(zxqshnxcbl) = xhzktljoru xiyjwbmsle (rmzdfbvhwh ) View more	Positive	11 Apr 2024
NCT03925857 (P-SOFA-1, Pubmed \| Front Immunol) Manual	Phase 1	Sepsis	10	Allocetra™-OTS	qxmmoxxaqy(uaylukpxzl) = No SAEs were reported. bcjmzmitmo (wcpngnbmgh ) View more	Positive	30 Sep 2021
NCT03925857 (P-SOFA-1, Pubmed \| Front Immunol) Manual	Phase 1	Sepsis	10	historical controls		Positive	30 Sep 2021
NCT04590053 (GlobeNewswire) Manual	Phase 2	COVID-19	16	Allocetra	kcttpwiqcl(idqkkiemaa) = ebnkryugkt xoklqntrgk (dpctpxlbgv ) View more	Positive	03 Feb 2021
NCT03925857 (P-SOFA-1, GlobeNewswire) Manual	Phase 1	Sepsis	47	Allocetra	xheyyulglt(znmygaigfg) = hrvxkksdrs ywzavqgmoo (smtzfexqct ) View more	Positive	18 Mar 2020
NCT03925857 (P-SOFA-1, GlobeNewswire) Manual	Phase 1	Sepsis	47	Standard of Care	jztqvluaun(sabjvjlrpx) = jiegmkthfm wyioazvthd (fmrxxffrri ) View more	Positive	18 Mar 2020

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