On May 31, 2022 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company, reported new preclinical data from an ovarian cancer study conducted in collaboration with Yale Cancer Center (Press release, Enlivex Therapeutics, MAY 31, 2022, View Source [SID1234615257]). The study showed substantial and statistically significant improvements in survival benefit, survival duration and tumor burden reduction when Allocetra was combined with an anti-PD1 checkpoint inhibitor. The data will be featured in an upcoming poster presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting, which is taking place both virtually and in-person at the McCormick Place convention center in Chicago, Illinois (United States) from June 3 – 7, 2022.

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The upcoming ASCO (Free ASCO Whitepaper) poster will also highlight a prior preclinical study in mesothelioma cancer that showed a substantial survival benefit when Allocetra was combined with a commercially approved anti-CTLA4 checkpoint inhibitor. Previously reported preclinical data in peritoneal cancer that show a substantial survival benefit when Allocetra is combined with chimeric antigen receptor (CAR) T-cell therapy will also be presented.

Marcus Bosenberg, MD, PhD, Professor of Dermatology, Pathology, and Immunobiology and Director of the Center for Precision Cancer Modeling at Yale Cancer Center, commented: "I am highly encouraged by these preclinical findings, which clearly demonstrate Allocetra’s potential to address a long-standing unmet need. The immunosuppressive microenvironments of ovarian tumors have limited the clinical benefits of checkpoint inhibition in this indication. Allocetra may reverse immunosuppressive tumor microenvironments and may ultimately improve patient outcomes by synergistically enhancing checkpoint inhibitor efficacy in clinical trials."

Prof. Dror Mevorach, MD, Chief Scientific Officer of Enlivex, added: "In these latest murine studies, we once again saw Allocetra synergistically combine with a checkpoint inhibitor to deliver a statistically significant survival benefit in a difficult-to-treat solid tumor model. We are now working to translate these promising findings to the clinic and expect to initiate two solid tumor trials evaluating Allocetra-based combinations by year-end. Through these studies, we aim to clinically demonstrate the broad applicability of Allocetra’s proposed mechanism of action to enable the expansion of its potential therapeutic impact."

Ovarian Cancer, Checkpoint Inhibitors, and Macrophage-Solid Tumor Dynamics

Ovarian cancer is currently the fifth leading cause of cancer death among women. Stand-alone therapy with PD1 checkpoint inhibitors, which are designed to treat cancer by activating immune cells that can identify and destroy tumors, has thus far shown limited efficacy in this indication. Prior clinical trials in ovarian cancer evaluating anti-PD1 monotherapy have shown response rates of only 7% – 15%.

The limited response rates of checkpoint inhibitors in ovarian and other solid cancers is linked to tumor defense mechanisms that facilitate the recruitment of macrophages which become "pro-tumor" tumor associated macrophages (TAMs) rather than "anti-tumor" macrophages. Pro-tumor TAMs typically form a physical layer on top of solid tumors and induce an immunosuppressive tumor microenvironment (TME). This in-turn promotes tumor growth and metastasis and makes it very difficult for immune cells or any anti-cancer drug to efficiently attack cancerous cells. Allocetra is a cell therapy in development that is targeted towards TAMs. Its proposed mechanism of action is to change the balance of macrophage populations so that they skew towards anti-tumor macrophages and away from pro-tumor macrophages. This is expected to enhance the efficacy of checkpoint inhibitors and other immunotherapeutic agents.

The Ovarian Cancer Model

To expand upon its previous preclinical findings in mesothelioma and test the potential effects of cell-therapy-induced macrophage reprogramming in a second difficult-to-treat solid tumor model, Enlivex collaborated with the Yale Cancer Center to run preclinical studies in which groups of mice were implanted with ID8 ovarian cancer cells. The difference between the groups was the treatment given, which started on day 7 after the cancer’s initial growth period.

Results from the preclinical ovarian cancer study further support Allocetra’s potential to significantly improve survival outcomes by facilitating macrophage reprogramming in the solid tumor microenvironment. Twelve weeks after the initial treatment, untreated mice (vehicle) showed a survival rate of 0%, and a median survival duration of 6 weeks. Survival duration was increased with stand-alone treatment with either an anti-PD1 inhibitor or Allocetra. The magnitude of the increases were similar between these two monotherapy groups (42% and 58% increase, respectively), with no significant effect on overall survival probability observed between the monotherapy groups. Notably, combining Allocetra with anti-PD1 therapy led to a synergistic anti-cancer effect, with survival rates of up to 50% (5/10) and an 83% increase in median survival duration observed in the combination therapy groups. The attached figure shows the Kaplan-Meier survival probability curve for each group of the study, and the table below provides the treatment data.

As previously reported, Enlivex plans to initiate a Phase Ib trial evaluating Allocetra in combination with chemotherapy in solid peritoneal tumors in Q3 2022, and a Phase I/II trial evaluating Allocetra in combination with an immune checkpoint inhibitor in late 2022.

The title of the upcoming ASCO (Free ASCO Whitepaper) poster is "In-vivo reprogramming macrophages and dendritic cells with Allocetra-OTS: Successful mono- and combination-antitumor therapy." The poster will be presented during the ASCO (Free ASCO Whitepaper) Annual Meeting’s "Developmental Therapeutics – Immunotherapy" poster session, which is taking place on June 5, 2022, from 8:00 AM – 11:00 AM CDT (9:00 AM – 12:00 PM ET). A copy of the poster’s corresponding abstract is currently available on the ASCO (Free ASCO Whitepaper) Annual Meeting Website.

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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.