First CAR T therapy leveraging combination of cell intrinsic PD1DNR checkpoint inhibition and 1XX CAR signaling technologies to enter the clinic
Atara's next-generation CAR T program targets Mesothelin, a highly-expressed antigen on the cell surface of many aggressive solid tumors
Evidence of preclinical safety, improved functional characteristics and enhanced antitumor efficacy of ATA2271 from IND-enabling studies were recently presented at the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting II
Atara Biotherapeutics, Inc. (NASDAQ:ATRA), a pioneer in T-cell immunotherapy leveraging its novel allogeneic EBV T-cell platform to develop treatments for patients with severe diseases including solid tumors, hematologic cancers and autoimmune disease, today announced that the U.S. Food and Drug Administration (FDA) has accepted the Investigational New Drug (IND) application providing clearance to initiate an open-label, single-arm Phase 1 clinical study of ATA2271, the Company's next-generation autologous CAR T therapy targeting mesothelin under development in collaboration with Memorial Sloan Kettering Cancer Center (MSK), for the treatment of advanced mesothelioma.
"We are pleased the FDA has cleared the IND for ATA2271 for the treatment of advanced mesothelioma," said Jakob Dupont, Global Head of Research and Development, Atara Biotherapeutics. "This milestone marks an important moment in the advancement of cell and gene immunotherapy for patients, for the field and for Atara. As the first-ever CAR T therapy leveraging the combination of PD1DNR checkpoint inhibition and 1XX CAR signaling technologies to enter the clinic, we are advancing such a unique CAR T program with the goal of developing transformative therapies for patients with solid tumors."
This novel next-generation autologous, mesothelin-targeted CAR T therapy was developed in collaboration with researchers at MSK, Dr. Prasad Adusumilli, who led two trials with first-generation mesothelin CAR T therapy and engineered T-cell intrinsic checkpoint blockade by PD1DNR to overcome the immune suppression of PDL1, and Dr. Michel Sadelain, a leader in the CAR T-cell field who developed the 1XX co-stimulatory domain technology to extend T-cell effector function while limiting cell exhaustion.
At the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting II, preclinical data were presented from ATA2271 IND-enabling studies conducted collaboratively in Dr. Adusumilli's laboratory, showing the effects of combining multiple novel technologies in this next-gen CAR T therapy, which includes both 1XX co-stimulatory domain signaling and an engineered PD1DNR. ATA2271 was associated with less cell exhaustion, improvements in functional persistence, serial cell killing, and enhanced in vivo efficacy when compared with first-generation mesothelin CAR T therapy. These effects were maintained through multiple redosings with ATA2271 and are consistent with emerging views in the field regarding preferred characteristics of CAR Ts when targeting solid tumors, including mesothelioma. This improved profile of ATA2271 will now be assessed in a Ph1 clinical trial led by principal investigator, Dr. Roisin O'Cearbhaill.
Although CAR T cell therapies have been approved for certain hematologic malignancies, they have not yet proven effective in solid tumor settings. Mesothelin is a tumor-specific antigen that is commonly expressed at high levels on the cell surface in many aggressive solid tumors including mesothelioma, ovarian cancer, pancreatic cancer, and non-small cell lung cancer. Atara has selected mesothelin as the target for both the ATA2271 autologous and the ATA3271 allogeneic programs along with novel CAR T-cell technologies that have the potential to further enhance activity and resulting clinical benefits. ATA3271, the allogeneic version of this CAR T, leverages Atara's EBV T-cell platform and is currently in IND-enabling studies.