GC027 / AstraZeneca - LARVOL DELTA

CD7 targeted "off-the-shelf" CAR-T demonstrates robust in vivo expansion and high efficacy in the treatment of patients with relapsed and refractory T cell malignancies. (PubMed, Leukemia) - "One patient had progression free survival of >3 years. With manageable toxicity profile, GC027 demonstrated superior clinical efficacy to standard chemotherapy regimens in (R/R) T cell malignancies."

Journal • Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CD7

Gracell drops 3 CAR-T programs in hopes of speeding more advanced assets to the finish line (Fierce Pharma) - "Gracell Biotechnologies is shaving down its CAR-T pipeline, throwing several programs out the window in an effort to speed its most advanced programs to the finish line...GC019F, a CD19 program targeting advanced B-cell acute lymphoblastic leukemia, has been cut. The CAR-T was being assessed in a phase 1 clinical trial. The second program left behind is GC027, an allogenic CAR-T designed to treat relapsed or refractory T-cell acute lymphoblastic leukemia. Lastly, Gracell dropped GC503, a mesothelin program designed to treat solid tumors...The company hopes to instead focus on the dual-targeting therapy GC012F derived from the company’s FasTCAR-T autologous platform made for next-day manufacturing....After completing a $150 million private placement financing earlier this month, Gracell anticipates its current cash will stretch into the second half of 2026, Chief Financial Officer Kevin Xie, Ph.D., said on the earnings call."

Commercial • Discontinued • Pipeline update • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Gynecologic Cancers • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Solid Tumor • T Acute Lymphoblastic Leukemia

Gracell Biotechnologies Reports Second Quarter 2022 Unaudited Financial Results and Provides Corporate Update (GlobeNewswire) - "GC012F: On track to submit the U.S. and China IND filings for r/r MM in the second half of 2022; GC027: TruUCAR-enabled CD7-targeted allogenic CAR-T cell therapy for the treatment of relapsed/refractory T cell acute lymphoblastic leukemia (r/r T-ALL). Target to have regulatory interactions globally and in China in the next 12 months."

Non-US regulatory • Regulatory • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • T Acute Lymphoblastic Leukemia

Gracell Biotechnologies Announces Multiple Advancements of TruUCAR Allogeneic CAR-T Platform (PRNewswire) - "Gracell Biotechnologies...announced multiple advancements of its TruUCAR platform, the Company's proprietary technology platform designed to generate high-quality allogeneic CAR-T cell therapies that can be administered 'off-the-shelf' as stand-alone therapy at lower cost and with greater convenience....An abstract providing early results of a first-in-human clinical study on GC502 in r/r B-ALL patients has been accepted for poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2022....'In addition, enrollment on the IIT for GC027 in patients with T-ALL will be concluded to summarize the clinical findings'."

Clinical data • Enrollment status • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

Preclinical Results of an Allogeneic, Universal CD19/CD7-Targeting CAR-T Cell Therapy (GC502) for B Cell Malignancies (ASH 2021) - "It demonstrated robust anti-tumor efficacy and promising potentials to suppress HvG. This report presents an example that the dual CAR design of GC502 may serve as a novel “off-the-shelf” CAR-T technology."

CAR T-Cell Therapy • IO biomarker • Preclinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CD19 • CD7 • IFNG • IL2 • TNFA

Gracell Biotechnologies Reports Second Quarter 2021 Unaudited Financial Results and Provides Corporate Update (GlobeNewswire) - “GC012F for the treatment of multiple myeloma (MM)…GC027 for the treatment of adult relapsed/refractory T cell acute lymphoblastic leukemia (r/r T-ALL)…IND in 2022. IND application submission in both the US and China planned in 2022…Research and development expenses for the three months ended June 30, 2021 were RMB65.3 million (US$10.1 million), as compared to RMB40.8 million in the corresponding prior year period.”

Commercial • IND • Non-US regulatory • Acute Lymphocytic Leukemia • Hematological Malignancies • Multiple Myeloma • Oncology • T Acute Lymphoblastic Leukemia

Anti-CD7 U-CAR-T Cell Therapy for T/NK Cell Hematologic Malignancies (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Xinqiao Hospital of Chongqing; Not yet recruiting ➔ Recruiting; Trial completion date: Apr 2022 ➔ Jun 2023; Trial primary completion date: Apr 2021 ➔ Jun 2022

CAR T-Cell Therapy • Clinical • Enrollment open • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • CD7

[VIRTUAL] Updates on clinical safety and efficacy result of GC027, the first-in-human, “Off-the-Shelf” CD7 CAR-T stand-alone therapy for adult patients with relapsed/refractory T-cell lymphoblastic leukemia (r/r T-ALL) (AACR 2021) - "The allogeneic off-the-shelf TruUCAR™ CAR-T GC027 shows promising efficacy as standalone therapy in heavily pretreated R/R T-ALL pts with a manageable safety profile. A single infusion of GC027 was able to induce deep, durable responses, with the longest duration of response (MRD-CR) 18 months post treatment still ongoing without any additional therapy during remission. GC027 warrants further evaluation in larger clinical studies."

Clinical • Late-breaking abstract • P1 data • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CD7 • CSF3

A Study of GC027 Injection in Relapse and Refractory T-ALL or T-LBL (clinicaltrials.gov) - P1; N=15; Not yet recruiting; Sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

Clinical • IO biomarker • New P1 trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CD7

Gracell Biotechnologies Reports Long-term Follow-up Data on TruUCAR-enabled GC027 in Relapsed/Refractory T-ALL at the AACR 2021 Annual Meeting (PRNewswire) - P1, N=6; “Gracell Biotechnologies Inc…presented updated long-term follow-up data on their TruUCAR-enabled allogeneic product candidate GC027 for the treatment of adult patients with relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) in an e-poster presentation at the 2021 American Association for Cancer Research (AACR) Annual Meeting on April 10… Patients had received a median of six prior lines of therapy and received a single infusion of TruUCAR GC027 in one of three dose levels: 0.6x107cells/kg, 1.0x107cells/kg or 1.5x107cells/kg. Six patients (100%) treated achieved a complete remission with or without complete blood count recovery (CR/CRi) and five of the six patients (83%) achieved minimum residual disease negative complete remission (MRD- CR)… Overall safety findings were consistent with previous observations.”

P1 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Oncology • T Acute Lymphoblastic Leukemia

Eradication of T-ALL cells by CD7 targeted universal CAR-T cells and initial test of ruxolitinib-based CRS management. (PubMed, Clin Cancer Res) - "Purpose：Although chimeric antigen receptor T cell (CAR-T) therapy development for B cell malignancies has made significant progress in the last decade, broadening the success to treating T-ALL has been limited. GC027- might have a potential to be a promising new approach for treating refractory/relapsed T - ALL. Further studies are warranted."

CAR T-Cell Therapy • Journal • Graft versus Host Disease • Immunology • Oncology • CD7

Gracell closes $100M series C round to advance CAR T-cell therapy candidates (Bioworld) - "Gracell Biotechnologies Inc. has closed a $100 million series C financing round to advance its CAR T-cell therapy candidates, including autologous product candidate, GC-012F, and allogeneic product candidate, GC-027. Both candidates are in investigator-initiated phase I trials in China."

Financing • New P1 trial • Oncology

Gracell Biotechnologies Raises 100 Million in Series C Funding to Advance Next Generation CAR-T Cell Therapies (PRNewswire) - "Gracell Biotechnologies Inc...today announced it has secured $100 million in Series C funding. The round is led by Wellington Management Company, OrbiMed and Morningside Ventures, and joined by new investor Vivo Capital. Existing investors Temasek Holdings, Lilly Asia Ventures, OrbiMed and King Star Med LP are also participating...Currently, Gracell's lead FasTCAR autologous product candidate, GC012F, is being studied in an ongoing investigator-initiated Phase 1 trial....TruUCAR allogeneic product candidate, GC027, is being studied in an ongoing investigator-initiated Phase 1 trial in China for the treatment of relapsed or refractory T cell acute lymphoblastic leukemia (r/r T-ALL)."

Financing • Hematological Malignancies • Multiple Myeloma • Oncology • T Acute Lymphoblastic Leukemia

[VIRTUAL] FIRST-IN-HUMAN, UNIVERSAL ANTI-CD7 CAR-T THERAPY FOR RELAPSED AND REFRACTORY T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (R/R T-ALL) (EHA 2020) - "GC027 has demonstrated superior clinical efficacy and induced deep response in patients with acceptable safety profile. The trial is ongoing and updated data will be presented at the meeting."

IO Biomarker • P1 data • Acute Lymphocytic Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD52

[VIRTUAL] Safety and efficacy results of GC027: The first-in-human, universal CAR-T cell therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). (ASCO 2020) - "With a single infusion of GC027, 80% of the patients had robust CAR-T cell expansion and achieved persistent MRD- CR without using any biologics as part of the preconditioning therapy or bridging to HSCT. The first-in-human, universal CAR-T therapy for r/r T-ALL, GC027 has demonstrated superior clinical efficacy and induced deep response in patients with acceptable safety profile. The trial enrollment is ongoing and updated data will be presented at the meeting."

CAR T-Cell Therapy • Clinical • P1 data • Acute Lymphocytic Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology

Gracell announces two presentations at the Annual Meeting of American Society of Clinical Oncology (ASCO) (PRNewswire) - "Gracell Biotechnologies Co., Ltd...announced that two presentations were accepted at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program. Both presentations can be found in the Development Therapeutics – Immunotherapy session, central on Gracell's TruUCAR™ GC027 in relapsed or refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) patients and EnhancedCAR GC008t in patients with advanced mesothelin-positive solid tumors."

Clinical data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

First human trial of off-the-shelf CAR T-cell therapy shows promise (ASH Clinical News) - "All 5 patients experienced similar serious adverse events to CAR T-cell therapies already in use, including cytokine release syndrome. 'The clinical benefit is limited by [that] high toxicity,' said AACR Program Committee Chair Antoni Ribas, MD..."

Media quote

Sending CAR T Cells after T-cell Malignancies. (PubMed, Cancer Discov) - "GC027, a new chimeric antigen receptor T-cell therapy manufactured with a proprietary allogeneic platform, TruUCAR, has shown effectiveness in a handful of patients with relapsed/refractory T-cell acute lymphoblastic leukemia, a disease with limited treatment options."

CAR T-Cell Therapy • Journal • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

[VIRTUAL] Clinical safety and efficacy study of TruUCAR™ GC027: The first-in-human, universal CAR-T therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) (AACR-I 2020) - "With a single infusion of GC027, 80% of the patients had robust CAR-T cell expansion and achieved persistent MRD- CR without using any biologics as part of the preconditioning therapy or bridging to HSCT. As the first-in-human, universal CAR-T therapy for adult r/r T-ALL, GC027 has demonstrated superior clinical efficacy and induced deep response in patients with acceptable safety profile. The trial enrollment is ongoing and updated data will be presented at the meeting."

Clinical • P1 data • IFNG • IL6

"新規ユニバーサルCAR-T療法TruUCAR GC027による成人の再発・難治性T-ALLのMRD-CR率は80％に【AACR2020】：がんナビ #AACR20 https://t.co/Aui7WmqeEa" (@cancer_navi)

Oncology

Gracell reports data of first-in-human clinical trial for universal TruUCAR GC027 in relapsed or refractory T-cell acute lymphoblastic leukemia at the AACR Virtual Annual Meeting (Businesswire) - P1, N=30; NCT04264078; "Gracell Biotechnologies Co., Ltd...has announced data of its first-in-human clinical trial for Universal TruUCAR™ GC027 in relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) patients...Treatment efficacy was assessed in five patients with 28 days of follow-up, of which: Five (100%) achieved a complete remission with or without complete blood count recovery (CR/CRi); Four (80%) achieved minimum residual disease negative complete remission (MRD-CR)."

P1 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Gracell to present the first-in-human, universal TruUCAR GC027 therapy for relapsed or refractory T-cell acute lymphoblastic leukemia at the AACR Annual Meeting (PRNewswire) - "Gracell Biotechnologies Co., Ltd...is pleased to announce that their first-in-human phase I data of Universal TruUCAR™ GC027 in relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) was accepted for plenary oral presentation at the America Association for Cancer Research (AACR) Annual Meeting."

P1 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology