Autolus Therapeutics plc, a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies for the treatment of cancer, today announced that the first patient has been dosed in its Phase 1/2 LibrA T1 clinical trial of AUTO4, a developmental therapy for the treatment of relapsed or refractory TRBC1-positive peripheral T cell lymphoma (PTCL). In addition, the company also announced that data on the preclinical sister program, AUTO5 targeting TRBC2-positive lymphoma, were presented at the 60th American Society of Hematology (ASH) Annual Meeting, San Diego. Autolus' T cell program comprises a companion diagnostic to determine whether the PTCL is TRBC1- or TRBC2-positive and two novel CAR T cell product candidates AUTO4 and AUTO5. PTCL is a rare and heterogeneous form of non-Hodgkin lymphoma, currently estimated to affect approximately 2,900 patients in the United States, annually.1

"There are limited treatment options for patients with relapsed and/or refractory peripheral T cell lymphoma. We are particularly excited to participate in the LibrA T1 trial of AUTO4, a novel CAR T cell therapy for this aggressive cancer," said Dr. Kate Cwynarski, Principal Investigator, Consultant Haematologist at University College London Hospital and Honorary Senior Lecturer at University College London.

"Effective systemic treatment for peripheral T cell lymphomas remains a challenge. CAR T therapies selectively targeting TRBC1-positive and TRBC2-positive T cell lymphomas have the potential to be major therapeutic advances," said Steven T. Rosen, M.D. provost and chief scientific officer of City of Hope and director of the Beckerman Research Institute of City of Hope.

On December 2 at the 60th ASH Annual Meeting in San Diego, the company presented data from preclinical studies of AUTO5 targeting TRBC2. TRBC1 and TRBC2 are virtually identical in sequence, and antibody binders had to be designed to differentiate TRBC1 from TRBC2 extracellular domains by selectively recognizing a single inversion of two amino acids. Employing a structural biology approach and molecular modelling techniques, a binder was generated that could bind TRBC2 without binding to TRBC1, and when included in a CAR T approach, selectively eliminated TRBC2-positive cells.

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