On September 12, 2022 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company, reported new preclinical data in a murine mesothelioma model showing a substantial and statistically significant survival benefit when Allocetra is combined with the chemotherapeutic agent, cisplatin (Press release, Enlivex Therapeutics, SEP 12, 2022, View Source [SID1234619416]). The data are featured in a poster being presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022, which is taking place both virtually and in-person at the Paris Expo Porte de Versailles in Paris, France from September 9, 2022 through September 13, 2022.
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Data featured in the ESMO (Free ESMO Whitepaper) poster are from preclinical studies in mice implanted with AB12 mesothelioma cells. Following implantation, mice were given vehicle (untreated group), intravenous (IV) cisplatin monotherapy, Allocetra monotherapy administered intraperitoneally (IP), or IV cisplatin in combination with IP Allocetra.
On day-57 post-implantation, the survival rate in the untreated group was 0%, and the mean survival duration was 31.7 ± 2.6 days. These were similar to the survival rate of 0% and slightly superior mean survival duration of 36.2 ± 5.0 days in the cisplatin monotherapy group. The survival rate and mean duration in the Allocetra monotherapy group were 14.2%, and 40.4 ± 10.9 days, respectively. When Allocetra was combined with cisplatin, a synergistic anti-cancer effect was observed, as the survival rate and mean duration in the combination therapy group were 55% and 49.3 ± 10.6 days, respectively. Notably, the increase in survival duration observed in the combination therapy group was statistically significant compared to the untreated group (p=0.0033, log rank), cisplatin monotherapy group ( p=0.0035, log rank), and Allocetra monotherapy (p=0.0413, log rank) group.
Also featured in the ESMO (Free ESMO Whitepaper) poster are preclinical mesothelioma data showing a substantial survival benefit when Allocetra is combined with an anti-PD1 checkpoint inhibitor, and previously presented preclinical data in mesothelioma showing a substantial survival benefit when Allocetra is combined with a commercially approved anti-CTLA4 checkpoint inhibitor.
"Our latest data add to an extensive body of preclinical evidence demonstrating Allocetra’s potential to address unmet needs in a variety of difficult-to-treat solid cancers," said Prof. Dror Mevorach, M.D., Chief Scientific Officer of Enlivex and co-author of the poster. "The disproportionate presence of pro-tumor macrophages in tumor microenvironments severely limits the efficacy of many drug classes, including both immuno- and chemotherapies. With Allocetra, we believe we can reprogram resident macrophages back to their homeostatic state, thereby enhancing the efficacy of complementary anti-cancer agents and avoiding the accumulation of pro-tumor macrophages. The data being presented at ESMO (Free ESMO Whitepaper) provide additional support for this hypothesis, as they highlight the potential benefits of combining Allocetra with cisplatin or immune checkpoint inhibitors such as anti-PD1 or anti-CTLA4. We look forward to discussing our findings with the medical community at this year’s congress."
Oren Hershkovitz, Ph.D., Chief Executive Officer of Enlivex, commented, "We are very pleased with the results of these preclinical studies, which support our ongoing Phase I/II trial evaluating Allocetra plus chemotherapy in patients with peritoneal metastases. This trial has been carefully designed to clinically demonstrate Allocetra’s novel mechanism of action and further our understanding of its safety profile and anti-cancer activity. Successfully achieving these goals would represent a key milestone, as it would bring us substantially closer to providing cancer patients with a novel and highly scalable next-generation cell therapy."
Mesothelioma, Treatment Landscape, and Macrophage-Solid Tumor Dynamics
Mesothelioma is one of the deadliest solid cancers, with the few available treatment options having limited efficacy. These include checkpoint inhibitors targeting CTLA4 and PD1, as well as cisplatin-based combinations. People most at risk for mesothelioma generally have had long-term exposure to asbestos (e.g., construction workers, pipe fitters, and shipyard workers).
In mesothelioma and other solid cancers, the efficacy of many anti-cancer agents is limited by tumor mechanisms that facilitate the recruitment of macrophages that 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 promote tumor growth and metastasis, thereby contributing to poor clinical outcomes and response to therapy. Allocetra is a cell therapy in development that targets these TAMs. Allocetra’s 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.
The ESMO (Free ESMO Whitepaper) poster (#479P) is titled, "Synergistic anti-tumor effect of Allocetra-OTS in combination with immune checkpoint inhibitors (ICI)/chemotherapy/CAR-T, through in-vivo reprogramming of macrophages." It is currently available for viewing on ESMO (Free ESMO Whitepaper)’s virtual platform and will also be presented by Prof. Mevorach, during Poster Session 13 of the ESMO (Free ESMO Whitepaper) Congress.
ABOUT ESMO (Free ESMO Whitepaper)
ESMO is a leading professional organization for medical oncology. Its core missions are to: (1) improve the quality of cancer care, from prevention and diagnosis all the way to palliative care and patient follow-up; (2) educate – doctors, cancer patients and the general public – on the best practices and latest advances in oncology; and (3) promote equal access to optimal cancer care for all patients.
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.