Nes-Ziona, Israel, May 09, 2022 (GLOBE NEWSWIRE) -- Enlivex Therapeutics Ltd. ( ENLV, the Company), a clinical-stage macrophage reprogramming immunotherapy company, announced the poster presentation of a substantial survival benefit of AllocetraTM combined with immune checkpoint inhibition in a preclinical mesothelioma study at the International Society of Cell and Gene Therapy Annual 2022 Meeting. The poster was titled, Allocetra-OTS, an Early Apoptotic Cellular Therapy Synergize with Chimeric Antigen Receptor (CAR) T Cell Therapy or Immune Check Point Inhibitor Against Peritoneal Solid Tumor.
Mesothelioma, Treatment Landscape, and Macrophage-Solid Tumor DynamicsMesothelioma is one of the deadliest solid cancers with few treatment options, all of which have limited efficacy. People who are most at risk to develop mesothelioma generally have had long-term exposure to asbestos (e.g., construction workers, pipe fitters, and shipyard workers). It takes many years for mesothelioma to develop; it can appear 30 years after asbestos exposure. Immune checkpoint inhibitors targeting CTLA4 and PD1 are FDA-approved as first-line treatments for patients with unresectable malignant pleural mesothelioma.
In mesothelioma and in some other solid cancers, tumor cells, as part of their defense mechanisms, facilitate the recruitment of macrophages which become pro-tumor tumor associated macrophages (TAMs) rather than anti-tumor macrophages. The TAMs typically form a physical layer on top of the solid tumor, and induce immunosuppression in the solid tumor microenvironment. This in-turn promotes tumor growth and metastasis and makes it very difficult for the immune system or any anti-cancer drug to efficiently attack the cancerous cells. Allocetra is a cell therapy in development that is targeted at these TAMs, and its proposed mechanism of action is to change the balance of macrophage populations to skew towards anti-tumor macrophages and away from pro-tumor macrophages.
The Mesothelioma Model
To test the potential effect of cell therapy-induced macrophage reprogramming on difficult-to-treat solid tumors, Enlivex ran preclinical studies in which five groups of mice were implanted with mesothelioma cancer cells. The difference between the groups was the treatment given, which started on day 12 after the cancers initial growth period.
Results from multiple studies strongly support the potential of AllocetraTM to assist in the process of macrophage reprogramming in the solid tumor microenvironment and significantly change survival outcomes. As expected, only 1/16 (6%) of the untreated mice remained alive at day 42 (that one last remaining mouse died on day 65), compared with up to 25% survival for the mice in the group that was treated with the anti-CTLA4 immune checkpoint inhibitor. Surprisingly, AllocetraTM as a stand-alone treatment provided comparable survival rates as anti-CTLA4 monotherapy, with a 28.5% survival rate and a delayed cancer growth rate observed. Notably, the synergistic effect of treating with both drugs resulted in up to 100% survival with complete disappearance of the cancer. The effect was correlated with the AllocetraTM treatment dose. A lower dose of AllocetraTM provided slightly lower survival and cancer complete remission rates (67% complete remission for the low-dose treatment vs. up to 100% for the higher dose). The attached chart provides a visual guide to the progressions/regression of the mesothelioma cancer in the different groups, as recorded for study mesothelioma AB12 137.
Across multiple studies of the AB12 mesothelioma model, anti-CTLA4 therapy significantly improved survival duration from mean 349 to 44.9 20 days (p<0.05). Allocetra as a stand-alone therapy improved survival duration to 52.3 20 days (p<0.02). The synergistic effect of the combination therapy of anti-CTLA4 + AllocetraTM improved survival duration to 86.720 days (p<0.0001) with complete cancer remission in 60-100% of mice, depending on the dose administered.
Prof. Dror Mevorach, Chief Scientific Officer of Enlivex, stated: This reproducible and statistically significant data strongly support Allocetras proposed therapeutic mechanism of action of reprogramming macrophages in solid tumors. We believe that, in contrast to CAR-T, CAR-NK and other anti-cancer cell therapies directed at tumor antigens, AllocetraTM restores macrophage homeostasis in the tumor environment via reprogramming of pro-tumor macrophages. This may ultimately allow immune checkpoint inhibitors to be exponentially more effective.
Oren Hershkovitz, Ph.D., CEO of Enlivex, added: Based on these results, Enlivex is planning to initiate a series of clinical trials during 2022 that are designed to evaluate Allocetra in combination with FDA-approved immune checkpoint inhibitor therapies in patients with advanced-stage solid tumors. To date, we have infused AllocetraTM in dozens of hospitalized patients in fragile condition resulting from sepsis and COVID-19-related organ dysfunction. We believe that the proposed differentiated mechanism of action of AllocetraTM, together with the safety and tolerability it has demonstrated in these prior studies, as well as the encouraging efficacy results of our preclinical solid tumor models, highlight an intriguing opportunity for Enlivex to provide another layer of life-saving therapy for patients who have few available options.
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 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.
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, ALLOCETRATM 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 Enlivexs 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 ALLOCETRATM 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 Enlivexs filings with the Securities and Exchange Commission, including in the Companys 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.
ENLIVEX CONTACT Shachar Shlosberger, CFO Enlivex Therapeutics, Ltd. [emailprotected]
INVESTOR RELATIONS CONTACTEric RibnerLifeSci Advisors[emailprotected]
Attachment
Here is the original post:
- Diagnosing Pleural Mesothelioma with Lung Fluid: The Battle of the Biomarkers - Surviving Mesothelioma - March 24th, 2017 [March 24th, 2017]
- Republican Health Care Bill Includes Asbestos Exposure Funding for Libby Residents - Mesothelioma.com - March 24th, 2017 [March 24th, 2017]
- Pembrolizumab shows promise in treatment of mesothelioma - Science Daily - March 24th, 2017 [March 24th, 2017]
- Veterans with Mesothelioma Benefit from Telephone Triage - Asbestos.com - March 24th, 2017 [March 24th, 2017]
- Mesothelioma Survival Rates Slowly Improving - Mesothelioma.net Blog (blog) - March 24th, 2017 [March 24th, 2017]
- Understanding Mesothelioma Caregiver Styles - Asbestos.com (blog) - March 24th, 2017 [March 24th, 2017]
- Mesothelioma Patients Turn to Cannabis - AlterNet - March 24th, 2017 [March 24th, 2017]
- Mesothelioma | Overview, Treatment Options and Survivor Stories - March 24th, 2017 [March 24th, 2017]
- Accelerated Approval Granted to Drug in Mesothelioma Research Pipeline - MesotheliomaHelp.org (blog) - April 8th, 2017 [April 8th, 2017]
- New Study Affirms Mesothelioma Survival Benefit with Post-Surgical IMRT, According to Surviving Mesothelioma - Benzinga - April 8th, 2017 [April 8th, 2017]
- The Key to Mesothelioma Treatment Success with Immunotherapy - Surviving Mesothelioma - April 8th, 2017 [April 8th, 2017]
- New Evidence Supports Post-Surgical IMRT for Mesothelioma Treatment - Surviving Mesothelioma - April 8th, 2017 [April 8th, 2017]
- Shorter Mesothelioma Survival Linked to High Platelet Count - Asbestos.com - April 8th, 2017 [April 8th, 2017]
- Mesothelioma Victims Center Now Appeals to All Diagnosed ... - Yahoo Finance - April 8th, 2017 [April 8th, 2017]
- Early research suggests first immunotherapy for mesothelioma on the horizon - Medical Xpress - June 6th, 2017 [June 6th, 2017]
- Bristol-Myers Squibb's Opdivo, Yervoy put the brakes on mesothelioma in phase 2 - FiercePharma - June 6th, 2017 [June 6th, 2017]
- Methanol from African Plants Kills Mesothelioma Cells - Asbestos.com - June 6th, 2017 [June 6th, 2017]
- Mesothelioma Patients to be Celebrated on National Cancer Survivor's Day - Mesothelioma.net Blog (blog) - June 6th, 2017 [June 6th, 2017]
- IO Strategy In Mesothelioma Finally Gets Mapped Out | Seeking Alpha - Seeking Alpha - June 6th, 2017 [June 6th, 2017]
- New Blood Test Could Mean Earlier Mesothelioma Diagnosis - Surviving Mesothelioma - June 6th, 2017 [June 6th, 2017]
- Using Viruses to Boost Mesothelioma Immunotherapy - Asbestos.com - June 6th, 2017 [June 6th, 2017]
- Resilience Can Help Mesothelioma Patients and Their Families ... - MesotheliomaHelp.org (blog) - June 7th, 2017 [June 7th, 2017]
- Janet Stanton Schnitzer Remembers Her Father's Mesothelioma Battle - Mesothelioma & Asbestos Awareness Center (blog) - June 7th, 2017 [June 7th, 2017]
- Treating Mesothelioma: A rare, aggressive caner - ABC2 News - June 7th, 2017 [June 7th, 2017]
- Asbestos and Mesothelioma Lawsuits: What to Expect | Nolo.com - June 7th, 2017 [June 7th, 2017]
- Mesothelioma Victims Center Now Urges a Roofer/Insulator With Mesothelioma to Call About Why It Is Necessary to ... - PR Newswire (press release) - June 9th, 2017 [June 9th, 2017]
- Mesothelioma Patients May Have Another Treatment Option With FDA Expanded-Use Approval of Lung Cancer Drug - MesotheliomaHelp.org (blog) - June 9th, 2017 [June 9th, 2017]
- A Breath Test for Mesothelioma? - Surviving Mesothelioma - June 9th, 2017 [June 9th, 2017]
- Mesothelioma Cancer: 12 Essential Facts - Asbestos News - June 9th, 2017 [June 9th, 2017]
- Mesothelioma - NHS Choices - June 9th, 2017 [June 9th, 2017]
- 15-year Mesothelioma Survivor Living Life By Design - Asbestos.com (blog) - June 9th, 2017 [June 9th, 2017]
- Mesothelioma Cancer Overview | Experienced Lawyers Here to Help - June 11th, 2017 [June 11th, 2017]
- Mesothelioma Victims Center Now Urges a Diagnosed Machinist to Call for Direct Access to Journeyman-Level ... - PR Newswire (press release) - June 12th, 2017 [June 12th, 2017]
- Honeywell Fails in Appeal Against Mesothelioma Verdict - Mesothelioma.net Blog (blog) - June 12th, 2017 [June 12th, 2017]
- Mesothelioma Patients Can See Improved Survival By Reporting Side Effects - MesotheliomaHelp.org (blog) - June 12th, 2017 [June 12th, 2017]
- What is Mesothelioma? | Surviving Mesothelioma - Surviving Mesothelioma - June 13th, 2017 [June 13th, 2017]
- Cases of Pleural Mesothelioma - Surviving Mesothelioma - June 13th, 2017 [June 13th, 2017]
- The Importance of Cancer Research in Immunotherapy - Mesothelioma.com (blog) - June 14th, 2017 [June 14th, 2017]
- Hopes High for Mesothelioma Immunotherapy Treatment ... - Mesothelioma.net Blog (blog) - June 14th, 2017 [June 14th, 2017]
- Asbestos Sprayers Face Higher Lifetime Mesothelioma Risk ... - Surviving Mesothelioma - June 14th, 2017 [June 14th, 2017]
- Remembering Loved Ones Lost to Mesothelioma, Looking Forward to Progress in Treatment - MesotheliomaHelp.org (blog) - June 14th, 2017 [June 14th, 2017]
- Chicago Public Schools Ignoring Asbestos Problem - Mesothelioma.com - June 16th, 2017 [June 16th, 2017]
- Length of Time Between Surgeries a Marker for Mesothelioma Survival - Surviving Mesothelioma - June 16th, 2017 [June 16th, 2017]
- Mesothelioma Survivor Deals with Pain 15 Years After Surgery - Asbestos.com (blog) - June 16th, 2017 [June 16th, 2017]
- Nivolumab and Ipillimumab Show Promise in Treating Mesothelioma Recurrence - Mesothelioma.com - June 16th, 2017 [June 16th, 2017]
- Mesothelioma Patients Should Heed FDA Warnings Regarding Miracle Cures - MesotheliomaHelp.org (blog) - June 16th, 2017 [June 16th, 2017]
- Mesothelioma Patients May Benefit from Marijuana Research - Mesothelioma.net Blog (blog) - June 17th, 2017 [June 17th, 2017]
- The Challenges of Research in Immunotherapy - Mesothelioma.com (blog) - June 17th, 2017 [June 17th, 2017]
- Despite Mesothelioma Diagnosis, Dad Loved Father's Day - Asbestos.com (blog) - June 17th, 2017 [June 17th, 2017]
- I Want to Keep Writing About Mesothelioma and My Family's Journey Because It Matters - MesotheliomaHelp.org (blog) - June 17th, 2017 [June 17th, 2017]
- Mesothelioma Clinical Trial Opens with High Expectations - Asbestos.com - June 17th, 2017 [June 17th, 2017]
- Cediranib May be Safe Supplement to Mesothelioma Treatment - Surviving Mesothelioma - June 17th, 2017 [June 17th, 2017]
- New Trial Finds VEGF-Inhibitor May Safely Boost Mesothelioma ... - Benzinga - June 18th, 2017 [June 18th, 2017]
- Mesothelioma Symptoms - Identify Early Warning Signs - June 18th, 2017 [June 18th, 2017]
- Mesothelioma Victims Center Now Urges a Diagnosed Construction Worker or Plumber to Call for Instant Access to the ... - PR Newswire (press release) - June 20th, 2017 [June 20th, 2017]
- Mesothelioma Treatment May Benefit From New Discovery ... - Mesothelioma.net Blog (blog) - June 20th, 2017 [June 20th, 2017]
- The Influence of BAP1 on Mesothelioma Survival - Surviving Mesothelioma - June 20th, 2017 [June 20th, 2017]
- Clinical Trial to Assess If Radiation Therapy Can Bring Effective Relief from Mesothelioma Pain - MesotheliomaHelp.org (blog) - June 20th, 2017 [June 20th, 2017]
- Asbestos Exposure Attorneys - Mesothelioma Lawsuits ... - June 20th, 2017 [June 20th, 2017]
- Can a Breath Test Diagnose Mesothelioma in the Early Stages? - Asbestos.com - June 21st, 2017 [June 21st, 2017]
- Mesothelioma Compensation Center Now Urges an Electric Utility Worker or Electrician with Mesothelioma to Aim High ... - PR Newswire (press release) - June 21st, 2017 [June 21st, 2017]
- Nurse Explains Mesothelioma Staging - MesotheliomaHelp.org (blog) - June 21st, 2017 [June 21st, 2017]
- 5 Questions: Treatment options exist for mesothelioma - Las Vegas Review-Journal - June 21st, 2017 [June 21st, 2017]
- Steve McQueen's Wife Pushes for Asbestos Ban - Mesothelioma.com - June 21st, 2017 [June 21st, 2017]
- Remembering Mesothelioma Victims in the UK - Mesothelioma.com (blog) - June 21st, 2017 [June 21st, 2017]
- Peritoneal Cancer Index: What it Means for Mesothelioma Patients - Mesothelioma & Asbestos Awareness Center (blog) - June 21st, 2017 [June 21st, 2017]
- Mesothelioma Risk Continues to Rise for Decades After Asbestos Exposure - Surviving Mesothelioma - June 21st, 2017 [June 21st, 2017]
- Nintedanib Combination Delayed Progression in Malignant Mesothelioma - Cancer Network - June 22nd, 2017 [June 22nd, 2017]
- Polish Study Confirms That Mesothelioma Risk Only Increases With ... - Mesothelioma.net Blog (blog) - June 22nd, 2017 [June 22nd, 2017]
- The Mesothelioma Victims Center Now Urges a Diagnosed Navy ... - PR Newswire (press release) - June 22nd, 2017 [June 22nd, 2017]
- Targeted Therapy May Soon be Primary Approach for Mesothelioma Treatment - MesotheliomaHelp.org (blog) - June 23rd, 2017 [June 23rd, 2017]
- Time Between Surgeries Helps Predict Mesothelioma Survival - Asbestos.com - June 23rd, 2017 [June 23rd, 2017]
- Testicular and Cardiac Mesothelioma - Surviving Mesothelioma - June 23rd, 2017 [June 23rd, 2017]
- Mesothelioma Veterans Center - Access Benefits & VA Claims - June 23rd, 2017 [June 23rd, 2017]
- Malignant Mesothelioma (Asbestos Cancer) > The Mesothelioma ... - June 23rd, 2017 [June 23rd, 2017]
- Mesothelioma Law Firm | Sokolove Law - June 23rd, 2017 [June 23rd, 2017]
- MicroRNAs May Be Key to Better Immunotherapy for Mesothelioma - Surviving Mesothelioma - June 24th, 2017 [June 24th, 2017]
- Mesothelioma Survival Rate | Factors Affecting Survivorship - June 24th, 2017 [June 24th, 2017]
- Scientists "Turn Off" Tumor-Protecting Protein in New Mesothelioma Study, According to Surviving Mesothelioma - Benzinga - June 26th, 2017 [June 26th, 2017]
- Symptoms of Mesothelioma - Critical Signs to Watch For - June 26th, 2017 [June 26th, 2017]