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Enterome announces sustained positive clinical outcomes with EO2401, its lead OncoMimics™ immunotherapy, in combination therapy in Glioblastoma at ASCO

On May 31, 2023 Enterome, a clinical-stage company developing first-in-class immunomodulatory drugs for cancer and inflammatory diseases based on its unique Mimicry platform, reported the presentation of new clinical data from its Phase 2 trial (ROSALIE) evaluating its lead OncoMimics immunotherapy candidate EO2401 in combination with an immune checkpoint inhibitor (nivolumab) +/- an anti-VEGF therapy with anti-edema properties (bevacizumab), in patients with first progression/recurrence of glioblastoma (GBM), at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Enterome, MAY 31, 2023, View Source [SID1234632268]). ASCO (Free ASCO Whitepaper) will take place June 2-6, 2023 in Chicago, Illinois.

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Nivolumab is used as an adjuvant to EO2401, to support T cell expansion and tumor infiltration. By itself, nivolumab has no observed clinical effect on GBM tumors. Bevacizumab was added to the treatment regimen to counteract immunosuppression by VEGF and to treat neurological symptoms and edema thought to be a result of tumor infiltration by immune cells.

Pierre Belichard, CEO at Enterome said, "We are thrilled with the clinical and immunological data emerging from the ROSALIE trial, which we are presenting at ASCO (Free ASCO Whitepaper). We are seeing elevated and durable increases in CD8+ T cell levels and a strong correlation to improved clinical outcomes for certain patients, particularly those receiving the triple combination of EO2401, nivolumab and bevacizumab. These findings, along with the broader insights gained from ROSALIE, pave the way to the next potentially pivotal stage in the clinical development of EO2401 in glioblastoma and for the advancement of our unique OncoMimics immunotherapy portfolio in solid and liquid tumors."

Key highlights from the Phase 2 ROSALIE trial poster presentation are:

Data published to date confirm that EO2401 in combination with nivolumab +/- bevacizumab is well tolerated with a safety profile consistent with the safety profiles of nivolumab and bevacizumab alone, with the addition of local administration site reactions.
Immune monitoring in peripheral blood demonstrated the ability of EO2401 to expand OncoMimic-specific CD8+ T cells with cross-reactivity against the targeted human tumor-associated antigens (TAAs) in a significant portion of patients. Memory specific CD8+ T cell responses were found as early as two weeks after the first vaccination and maintenance of a strong and stable immune response could be detected for up to 23 months.
EO2401 in combination with nivolumab generated strong systemic immune responses through activation of specific CD8+ T cells, correlating with clinical efficacy.
EO2401/nivolumab without efficacious anti-edema treatment shows the same efficacy as current standard of care with survival around nine months. Edema in some patients resulted in neurological symptoms leading to short treatment durations.
The addition of symptom-directed low-dose bevacizumab as an anti-edema treatment to EO2401/nivolumab prolonged treatment duration and improved all efficacy parameters (survival around 12.5 months).
EO2401/nivolumab with continuous standard bevacizumab added from the start further improved median treatment duration and efficacy (survival around 14.5 months).
Early data from final cohort (N=15) presented for the first time at ASCO (Free ASCO Whitepaper) gives hope regarding validation of the EO2401/nivolumab/bevacizumab triple combination regimen and outcome.
Patient enrollment was completed in late 2022. Further data will be presented in 2023.
Details on Enterome’s ROSALIE study (EOGBM1-18) poster presentation at ASCO (Free ASCO Whitepaper) are as follows:

Title: EO2401 (E) peptide immunotherapy + nivolumab (N) +/- bevacizumab (B) in recurrent glioblastoma (GB); EOGBM1-18/ROSALIE
Presenter: Wolfgang Wick, MD, Universitätsklinikum Heidelberg and German Cancer Research Center, Heidelberg, Germany
Track: Central Nervous System Tumors (Poster Board 377)
Abstract Number: 2020
Date and Time: Saturday, June 3, 1:15 – 4:15 PM CDT; Discussion 4.30 – 6:00 PM CDT
The abstract #2020 is available here.

About EO2401

EO2401 is Enterome’s first-in-class off-the-shelf OncoMimics peptide-based immunotherapy. It combines three microbial-derived OncoMimics peptides that closely mimic specific cytotoxic T cell (CD8+ T cell) epitopes on the Tumor-Associated Antigens IL13Ra2, BIRC5 and FOXM1, combined with the helper peptide (CD4+ T cell epitope) Universal Cancer Peptide 2 (UCP2). EO2041 is designed to trigger the immune system into recognizing these epitopes on glioblastoma cells as foreign (non-self) and eliciting a targeted memory T-cell driven cell-killing response against the tumor cells.

EO2401 is also being evaluated in a Phase 2 clinical trial in combination with nivolumab +/- bevacizumab, for the treatment of adrenal tumors (SPENCER study, EOADR1-19).

About ROSALIE

ROSALIE (EOGBM1-18, NCT04116658) is a multicenter, open-label, Phase 1/2 trial investigating EO2401 in combination with nivolumab +/- bevacizumab in patients with glioblastoma at first progression/recurrence after surgery and adjuvant radiotherapy/temozolomide. The trial is assessing safety, tolerability, immunogenicity and preliminary efficacy in 100 patients at centers in the US and Europe. Patient enrollment was completed in late 2022.

Enlivex Selected for an Elevator Pitch Presentation and two additional Poster Presentations at the 2023 Annual Meeting of the International Society for Cell & Gene Therapy

On May 31, 2023 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company targeting diseased macrophages, reported three poster presentations, including a selected Elevator Pitch Presentation at the 2023 Annual Meeting of the International Society for Cell & Gene Therapy (ISCT), which is taking place from May 31, 2023 through June 03, 2023 in Paris, France (Press release, Enlivex Therapeutics, MAY 31, 2023, View Source [SID1234632267]).

The poster (ID#805) presentation, "DEVELOPMENT OF A FROZEN FORMULATION OF ALLOCETRA-OTS, AN INNOVATIVE MACROPHAGE REPROGRAMMING CELL-BASED THERAPY", which details the development and regulatory acceptance of Allocetra frozen formulation, was selected for presentation at the Elevator Pitch Session on Wednesday, May 31, 2023 from 7:00 PM to 8:00 PM CEST, session room 241.

The second poster (ID#1003) presentation, "IN VITRO BIOLOGICAL ACTIVITY CHARACTERIZATION AND CELL BASED POTENCY ASSAY DEVELOPMENT FOR ALLOCETRA OTS", will take place on June 1, 2023 from 6:00 PM to 7:30 PM CEST.

The third poster (ID#1057) presentation, "SYNERGISTIC PERITONEAL ANT-TUMOR EFFECT OF ALLOCETRA-OTS, A CELLULAR IMMUNE THERAPY , IN COMBINATION WITH IMMUNE CHECKPOINT INHIBITORS/CHEMOTHERAPY THROUGH REPROGRAMMING OF MACROPHAGES AND DENDRITIC CELLS", will take place on June 1, 2023 from 6:00 PM to 7:30 PM CEST.

ABOUT THE INTERNATIONAL SOCIETY FOR CELL & GENE THERAPY

The International Society for Cell & Gene Therapy (ISCT) is a global society of clinicians, regulators, researchers, technologists, and industry partners with a shared vision to translate cell and gene therapy into safe and effective therapies to improve patients’ lives worldwide. For more information visit View Source

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.

Corvus Pharmaceuticals to Present at the Jefferies Healthcare Conference

On May 31, 2023 Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, reported that Richard A. Miller, M.D., president and chief executive officer of Corvus, will conduct one-on-one meetings with investors and present a corporate overview at the Jefferies Healthcare Conference, which is being held in New York from June 7-9 (Press release, Corvus Pharmaceuticals, MAY 31, 2023, View Source [SID1234632264]). The presentation will be on Wednesday, June 7, 2023 at 9:30 am ET.

A webcast of the presentation will be available live and for 90 days following the event. The webcast may be accessed via the investor relations section of the Corvus website.

Circio invites to a company update on Thursday 15 June 2023

On May 31, 2023 Circio Holding ASA (OSE: CRNA) Circio’s management reported that it will live webcast on Thursday 15 June at 10am CEST. In the webcast, CEO Erik D. Wiklund will provide a brief company update, followed by a Q&A session (Press release, Circio, MAY 31, 2023, View Source [SID1234632263]).

Date: Thursday 15 June 2023
Time: 10.00 CET
Webcast link: Click here to join the meeting
Presenter: Erik Digman Wiklund, CEO

Please submit any questions in advance to [email protected] or directly during the live webcast.

Questions can be made in English or Norwegian and will be addressed in the respective language.

Cellectis Publishes an Article in Cancer Immunology Research Demonstrating Preclinical Evidence of UCART20x22 Product Candidate to Target a Broad Spectrum of Patients with B-cell Malignancies

On May 31, 2023 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported an article in Cancer Immunology Research demonstrating pre-clinical proof-of-concept data of UCART20x22 product candidate, Cellectis’ first allogeneic dual CAR T-cell targeting the CD20 and CD22 antigens, to overcome current mechanisms of resistance to CAR T-cell therapies in B-cell Non-Hodgkin lymphoma (B-NHL), while providing a potential alternative to CD19 directed therapy (Press release, Cellectis, MAY 31, 2023, View Source [SID1234632262]).

B-cell Non-Hodgkin lymphoma (B-NHL) remains one of the most common cancers worldwide, with reports an estimate of 544,000 new cases and 260,000 deaths worldwide in 2020. Despite the groundbreaking efficacy of current CAR T-cell therapies, studies on patients treated with autologous CAR T-cells are revealing several causes for relapses that includes: antigen loss, low antigen expression or insufficient CAR T-cell potency and persistence, among others. While several suitable targets to treat B-cells malignancies have been identified, CD19 has been the focus of attention leading to a crowded space with limited therapeutic alternatives for CD19 low or negative relapses.

The limited amount of eligible treatment options after relapse from autologous CAR T-cell therapy or for patients not eligible for autologous therapies, underscores the urgent need to develop novel therapies with the potential to improve patient outcome.

To address these challenges, Cellectis developed UCART20x22, its first allogeneic dual CAR T-cell product candidate targeting two validated antigens commonly expressed in B-cell malignancies, CD20 and CD22, and whose expression is preserved after CD19 CAR T-cell treatment. Cellectis provides pre-clinical proof of concept demonstrating potent and sustained activity of different designs of allogeneic CD20xCD22 CAR in vitro and in vivo against various antigen combinations and models recapitulating antigen escape, a current challenge in the field that can lead to treatment failure. Moreover, UCART20x22 is developed to be available off-the-shelf and to offer a solution for patients whose T-cells are not functional or for which autologous manufacturing fails.

"In this study, we demonstrate that allogeneic CD20x22 CAR T-cells exhibit robust, sustained and dose-dependent activity in vitro and in vivo, while efficiently targeting primary Non-Hodgkin Lymphoma samples with heterogeneous levels of CD22 and CD20" said Beatriz Aranda Orgilles, Ph.D., Team Leader at Cellectis. "We are very excited to share these encouraging preclinical data that support the transition of UCART20x22 into the clinic and represent a potential therapeutic alternative to CD19-directed therapies."

Preclinical data showed that:

– The use of a bicistronic vector favors the generation of dual CAR T-cells co- expressing both CD20 and CD22 CARs

– CAR T-cells efficiently and persistently eradicate double positive tumor cells over time. More importantly, compared to the single CAR, the dual CAR displayed similarly strong cytolytic activity over time against tumor cells expressing a single antigen, validating the benefit of using a dual CAR approach.

– Both CD20xCD22 CAR versions tested in this study potently targeted tumor cells in vivo in a dose dependent manner, with both doses of 3 and 10 million CAR T-cells achieving complete tumor clearance.

– Xenograft models mimicking antigen escape with an aggressive lymphoma model demonstrate that the dual CD20xCD22 CAR is capable to eliminate all tumors despite of losing one antigen, thus providing a potential solution for this challenge in the field.

– Bone marrow and spleen analysis of the surviving animals treated with the dual CAR at the end of the study, revealed that dual CAR T-cells efficiently eradicated the tumor and are capable to persist in the bone marrow for longer than one hundred days

– Primary NHL samples with variable levels of CD20 and CD22 can successfully be eradicated with the dual CD20xCD22 CAR suggesting that UCART20x22 has the potential to reach a large patient population.

– Full tumor elimination is achieved in a dose dependent manner in a Patient-Derived Xenograft (PDX) model recapitulating mantle cell lymphoma at day 20 with a dose of 3 million CAR T-cells or higher.

UCART20x22 features TALEN-mediated disruptions of the TRAC gene (to minimize the risk of graft-versus-host disease) and of the CD52 gene (to permit use of a CD52-directed monoclonal antibody in patients’ lymphodepletion regimen) to enhance CAR T engraftment, expansion and persistence. UCART20x22 is Cellectis’ first product candidate fully designed, developed and manufactured in-house at Cellectis.

UCART20x22 is evaluated in the NATHALI-01 Phase 1/2a clinical study in patients with r/r B-NHL (NCT05607420).

This article is available on Cancer Immunology Research website by clicking on this link: View Source