FDA Grants IND of ARTEMIS™ T cell Platform To Enhance CAR-T Cancer Therapies Without Cytokine Storm

MedicalResearch.com Interview with:
Dr. Cheng Liu PhD
President and Chief Executive Officer of Eureka Therapeutics.

MedicalResearch.com: What is the background for this study? What are the main findings?

 

    • Eureka Therapeutics, Inc. is a clinical stage biotechnology company focused on improving the safety profile of T cell therapies and developing novel T cell therapies for the treatment of solid tumors.
    • ET190L1-ARTEMISTM utilizes Eureka’s proprietary ARTEMISTM T cell receptor platform and proprietary human anti- CD19 binder to target CD19-positive malignancies. In preclinical studies, ET190L1-ARTEMISTM matched the cancer killing potency of current CAR-T therapies but with a dramatic reduction in the levels of inflammatory cytokines released, a main cause of cytokine release syndrome. In addition, these studies have shown that ET190L1-ARTEMISTM T cells are less exhausted and more naive and therefore, expected to have improved persistence in vivo. If confirmed in the clinic, this could result in a longer term therapeutic benefit to patients with an improved safety profile.
    • Eureka is also focused on developing the next evolution of T cell therapies against solid tumors which represent 90% of all cancers. While CAR-T therapies have been successful with liquid tumors such as leukemia and lymphoma, they have not been successful in solid tumors because of a lack of specific cell surface antigens. Eureka has pioneered the use of TCR mimic antibodies to target intracellular antigens in solid tumors that were once considered undruggable. Using its proprietary human E-ALPHA® phage display library, Eureka has discovered highly-specific, high affinity TCR mimic antibodies that can target intracellular antigens in solid tumors when processed into peptides and presented onto the cell surface by the MHCI complex. Pre-clinical studies have shown that when these TCR mimic antibodies were engineered onto the ARTEMISTM or CAR-T cell receptor platform against hepatocellular carcinoma (liver cancer) cells, the T cells launched a potent anti-tumor response.

MedicalResearch.com: What is meant by cytokine storm? How will ET190L1-ARTEMIS™ T cells reduce this potentially devastating side effect of CAR-T therapies?

    • Cytokine stock (also known as cytokine release syndrome (CRS)) and neurotoxicity have been identified as significant safety issues plaguing current CAR-T therapies. More than 50% of CAR-T patients in some studies have exhibited serious Grade 3 or 4 levels of CRS which can mean a trip to the intensive care unit with associated neurological events, coagulation, and life-threatening infections.
    • Reducing the excessive overproduction of cytokines (the “cytokine storm”) while maintaining their cancer killing potency will not only make T cell therapies safer for patients, but could broaden the accessibility of these therapies to previously excluded classes of patients, permit use in earlier lines of treatment, allow repeat dosing, as well as to reduce their overall cost.
    • While the current belief is that CRS is a “necessary evil” and is coupled with efficacy, we believe our ARTEMISTM T cell platform may be cabable of turning conventional wisdom on its head. Unless this problem is solved, T cell therapy will be severely limited to only a handful of specialty cancer centers that are equipped to handle this dangerous side-effect.
    • In November 2017, Eureka received FDA IND approval to launch a Phase 1 clinical trial of ET190L1- ARTEMIS™, which utilizes Eureka’s proprietary ARTEMIS™ T-cell platform and proprietary human anti-CD19 binder to target CD19-positive malignancies.
    • The Phase 1 study will be led by Dr. David Rizzieri, Chief of Hematologic Malignancies at Duke Cancer Institute, Duke University School of Medicine. Eureka plans to enroll the first patient in this trial in the first quarter of 2018.
    • Preclinical studies show that T-cells equipped with ARTEMIS™ have the same potency as CAR-T therapies, minus cytokine storm. We believe CAR-T overstimulates the production of cytokines. Our proprietary ARTEMIS™ T cell platform was designed to utilize the T cell’s natural switching mechanism which enables it to produce just enough cytokines to kill the cancer cells, and then to down regulate the production when not in use.

MedicalResearch.com: What should readers take away from your report?

    • Eureka aims to prove in the Duke Phase I clinical trial that its ARTEMISTM T cell technology can match the cancer killing potency of CAR-T therapies against CD-19 positive malignancies, but without the serious side effects of CRS and neurotoxicity that is commonly observed in CAR-T therapies.
    • The Principal Investigator for the Phase I clinical trial is David A. Rizzieri, M.D., Professor of Medicine, Section Chief of Hematologic Malignancies and Associate Director for Clinical Research at the Duke Cancer Institute, Duke University School of Medicine.
    • If successful, Eureka hopes to apply our ARTEMISTM T cell technology to a broader class of patients than can be treated with CAR-T therapies, as well as to lower their overall cost. We are encouraged by the preclinical findings and look forward to quickly moving our therapy into clinical development as we continue to enhance our proprietary ARTEMISTM platform of innovative T cell therapies for both liquid and solid tumors. 

MedicalResearch.com: Is there anything else you would like to add?

    • Eureka is focused on developing the next evolution of T cell therapies by tackling the T cell industry’s two biggest challenges –improving patient safety and treating solid tumors. 

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Eureka Announces FDA Allowance of Investigational New Drug Application for ET190L1-ARTEMIS™ T cell Therapy in Relapsed and Refractory CD19+ Non-Hodgkin Lymphoma

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

 

 

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