OriCAR-017 / Oricell - LARVOL DELTA

Yuanqi Bio was invited to attend the JP Morgan Global Healthcare Annual Conference for the second time to report the latest progress of OriCAR-017 and Ori-C101 [Google translation] (Oricell Press Release) - "In his speech, Tom Farrell, the new president of YuanQi Bio, gave a detailed introduction to the company's proprietary platform, the latest progress of its R&D pipeline, its global layout and future development plans...In the field of multiple myeloma, OriCAR-017, the core project of Yuanqi Bio, as a CAR-T therapy targeting GPRC5D, continues to demonstrate best-in-class clinical potential among similar targeted therapies in the world...At the same time, Yuanqi Bio has also made significant progress in the field of solid tumors. At the conference, it presented the best-in-class data of another core project, Ori-C101, which is expected to bring breakthrough efficacy and lasting treatment effects to hepatocellular carcinoma (HCC) patients around the world....The company will accelerate the clinical development of OriCAR-017 in the United States and plans to advance multiple next-generation CAR-T therapies to the clinical validation stage in China."

Pipeline update • Hepatocellular Cancer • Multiple Myeloma • Solid Tumor

Strategic optimization of BCMA and GPRC5D dual-targeted CAR T cells for heterogeneous multiple myeloma (SITC 2024) - "GPRC5D CAR-T cells have mitigated BCMA escape-mediated relapse in murine models, thereby demonstrating their potential in addressing this clinical challenge...1S cells at an E:T ratio of 1:1Download figure Open in new tab Download powerpoint Abstract 267 Figure 3 OriCAR002 T cells exhibited superior functional advantage in vitro...(B) Theoretical single combination pattern of the an- ti-GPRC5D VHH and GPRC5D on MM cells. (C) Theo- retical double-binding pattern of the bispecifc Ori- CAR002 to BCMA and GPRC5D on MM cells"

CAR T-Cell Therapy • Heterogeneity • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • GPRC5D

Strategic optimization of BCMA and GPRC5D dual-targeted CAR T cells for heterogeneous multiple myeloma (SITC 2024) - "GPRC5D CAR-T cells have mitigated BCMA escape-mediated relapse in murine models, thereby demonstrating their potential in addressing this clinical challenge...1S cells at an E:T ratio of 1:1Download figure Open in new tab Download powerpoint Abstract 267 Figure 3 OriCAR002 T cells exhibited superior functional advantage in vitro...(B) Theoretical single combination pattern of the an- ti-GPRC5D VHH and GPRC5D on MM cells. (C) Theo- retical double-binding pattern of the bispecifc Ori- CAR002 to BCMA and GPRC5D on MM cells"

CAR T-Cell Therapy • Heterogeneity • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • GPRC5D

Strategic optimization of BCMA and GPRC5D dual-targeted CAR T cells for heterogeneous multiple myeloma (SITC 2024) - "GPRC5D CAR-T cells have mitigated BCMA escape-mediated relapse in murine models, thereby demonstrating their potential in addressing this clinical challenge...1S cells at an E:T ratio of 1:1Download figure Open in new tab Download powerpoint Abstract 267 Figure 3 OriCAR002 T cells exhibited superior functional advantage in vitro...(B) Theoretical single combination pattern of the an- ti-GPRC5D VHH and GPRC5D on MM cells. (C) Theo- retical double-binding pattern of the bispecifc Ori- CAR002 to BCMA and GPRC5D on MM cells"

CAR T-Cell Therapy • Heterogeneity • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • GPRC5D

Yuanqi Bio: CAR-T therapy obtains FDA fast track qualification [Google translation] (163.com) - "...July 16, according to the official website of Yuanqi Bio, the U.S. Food and Drug Administration has granted Yuanqi Bio's GPRC5D-targeted CAR-T cell injection (OriCAR-017) fast track qualification for the treatment of relapsed/refractory multiple myeloma. Obtaining this qualification will help OriCAR-017 accelerate clinical trials and market registration progress."

Fast track • Hematological Malignancies • Multiple Myeloma • Oncology

OriCAR-017, a novel GPRC5D-targeting CAR-T, in patients with relapsed/refractory multiple myeloma: Long term follow-up results of phase 1 study (POLARIS). (ASCO 2024) - P1 | "The updated results showed OriCAR-017 continued to provide deep and durable responses, MRD negativity was achieved in all RRMM pts, including in pts refractory to anti-CD38, PIs and IMIDs and failure to BCMA-directed therapy with excellent safety profile. The results of long-term efficacy and safety follow up support that OriCAR-017 is highly probable to be developed as a promising therapy in RRMM. Further clinical development efforts are undertaking to confirm the clinical benefits of OriCAR-017."

Clinical • IO biomarker • P1 data • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Novel Coronavirus Disease • Oncology • GPRC5D • SDC1

OriCAR-017 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of R/RMM (clinicaltrials.gov) - P1/2 | N=83 | Recruiting | Sponsor: OriCell Therapeutics Co., Ltd. | Enrolling by invitation ➔ Recruiting

Enrollment status • Hematological Malignancies • Multiple Myeloma • Oncology

2024 ASCO｜OriCAR-017 oral presentation abstract released by Yuanqi Bio [Google translation] (Oricell Press Release) - P1 | N=15 | NCT05016778 | "Oricell Bio announced that the abstract of the 2- year long-term follow-up results of its Phase I clinical trial of CAR-T drug (OriCAR-017) targeting GPRC5D in the treatment of relapsed/refractory multiple myeloma (RRMM) has been publicly released on the official website of the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract ID: 7511)...As of January 16 , 2024 , all ( 10 ) patients responded well to OriCAR-017 treatment, and the last patient has completed 24 months of follow-up. The overall response rate (ORR) was 100.0% , the strict complete response rate ( sCR ) was 80.0% , and the very good partial response rate (VGPR) was 20.0%....There were no pharmacokinetic differences between dose levels, with Cmax of 7354.7 copies/μL and AUC0-28 days of 68587 copies day/μg"

P1 data • PK/PD data • Hematological Malignancies • Multiple Myeloma • Oncology

Oricell Presented Long-term Follow-up Data of OriCAR-017 in RRMM at 2024 ASCO Annual Meeting, Highlighting the Sustained Efficacy of GPRC5D CAR-T Therapy (PRNewswire) - P1/2 | N=83 | NCT06182696 | Sponsor: OriCell Therapeutics Co., Ltd. | "As of January 16, 2024, all ten patients responded well to OriCAR-017, with the last patient having completed a 24-month follow-up. The overall response rate (ORR) was 100.0%, with a stringent complete response rate (sCR) of 80.0% and a very good partial response rate (VGPR) of 20.0%. All patients achieved 100% minimal residual disease negativity (MRD) at day 28, which was further confirmed as 100% negative at the 3-months follow-up.... In the high-dose group, where 67% of patients were previously treated with BCMA CAR-T, the mDoR was 17.23 months (95% CI, 7.33-NR), and the mPFS was 19.10 months (95% CI, 8.30-NR). Currently, a BCMA CAR-T-treated patient is still in remission (>24 months)."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

A Study to Evaluate the Safety, PK/PD of (OriCAR-017) in Subjects With RR/MM - RIGEL Study (clinicaltrials.gov) - P1 | N=81 | Recruiting | Sponsor: OriCell Therapeutics Co., Ltd. | Not yet recruiting ➔ Recruiting | Trial completion date: Apr 2026 ➔ Apr 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2026

CAR T-Cell Therapy • Enrollment open • Trial completion date • Trial primary completion date • Cardiovascular • Hematological Disorders • Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma • Oncology • Plasmacytoma

OriCAR-017 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of R/RMM (clinicaltrials.gov) - P1/2 | N=83 | Enrolling by invitation | Sponsor: OriCell Therapeutics Co., Ltd. | Recruiting ➔ Enrolling by invitation

Enrollment status • Hematological Malignancies • Multiple Myeloma • Oncology

A Study to Evaluate the Safety, PK/PD of (OriCAR-017) in Subjects With RR/MM (clinicaltrials.gov) - P1 | N=81 | Not yet recruiting | Sponsor: OriCell Therapeutics Co., Ltd.

New P1 trial • Cardiovascular • Hematological Disorders • Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma • Oncology • Plasmacytoma

GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review. (PubMed, Blood Cancer J) - "We review the biology and target validation of GPRC5D, and clinical data from early phase trials of GPRC5D-targeting bispecific antibodies, talquetamab and forimtamig, and chimeric antigen receptor T cell (CAR-T) therapies, MCARH109, OriCAR-017, and BMS-986393...Further clinical trials, including those investigating GPRC5D-targeting T-cell-redirecting agents in combination with other anti-myeloma therapies and with different treatment modalities, may help to elucidate the future optimal treatment regimen and sequence for patients with multiple myeloma and improve survival outcomes. Video Summary."

Journal • Review • Dermatology • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology

Oricell Announces FDA Clearance of IND Application for OriCAR-017, a novel GPRC5D Targeted CAR-T Cell Therapy Utilizing the Company's Proprietary Platform, for the Treatment of Relapsed/Refractory Multiple Myeloma. (PRNewswire) - "Oricell Therapeutics...today announced that the U.S. Food and Drug Administration (FDA) has cleared the company's Investigational New Drug (IND) application for OriCAR-017 for patients with relapsed/refractory multiple myeloma (R/R MM). OriCAR-017 is a chimeric antigen receptor (CAR) T cell therapy targeting GPRC5D....The IND enables Oricell to initiate the clinical development for OriCAR-017 in the US immediately."

IND • Hematological Malignancies • Multiple Myeloma • Oncology

OriCAR-017 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of R/RMM (clinicaltrials.gov) - P1/2 | N=83 | Recruiting | Sponsor: OriCell Therapeutics Co., Ltd.

New P1/2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Optimization of GPRC5D-targeted CAR T cells (OriCAR-017) for multiple myeloma (SITC 2023) - P1 | "Results We further demonstrated that GPRC5D CAR T-cells with tandem biepitopic VHHs (OriCAR-017) have superior MM cell lysis in vitro, low toxicity and high anti-tumor effects in vivo, compared to single VHH or bicistronic VHH structures (figures 1–5)...gov identifier: NCT05016778) with 10 MM patients, including 5 patients who had relapsed after BCMA CAR-T therapy, showed a 100% objective response rate without severe side effects with OriCAR-017 treatment, suggesting the safety and efficacy of OriCAR-017 therapy with best-in-class potential (figure 6). Conclusions Therefore, OriCAR-017 holds promise for the treatment of MM, either as a first-line therapy or for patients who have relapsed after BCMA CAR T-cell therapy (figure 7)."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology

Oricell OriCAR-017 CAR-T Therapy Clears IND Hurdle, Paving the Way for Global Impact (PRNewswire) - "August 10, 2023, in a groundbreaking development, Oricell Therapeutics...has received the green light for its Investigational New Drug (IND) application of OriCAR-017, a cutting-edge CAR-T cell therapy targeting GPRC5D to combat relapsed or refractory multiple myeloma (R/R MM). This remarkable milestone not only marks the world's first tier GPRC5D-targeting CAR-T therapy approved in China but also underlines Oricells prowess as a frontrunner in the biotech industry."

New trial • Hematological Malignancies • Multiple Myeloma • Oncology

Phase I open-label single arm study of GPRC5D CAR T-cells (OriCAR-017) in patients with relapsed/refractory multiple myeloma (POLARIS). (ASCO 2022) - P1 | "Patient received lymphodepleting chemotherapy with fludarabine 30mg/m2/d and cyclophosphamide 300mg/m2/d for 3 days followed by a single infusion of OriCAR-017...All CRSs were rapidly relieved after conventional intervention(tocilizumab and steroids)... In this phase I study, OriCAR-017 was showed safe and impressive efficacy in RRMM patients. Majority of AEs were transient and manageable. 100% ORR and 100% MRD negative rate, along with favorable safety support OriCAR-017 to be a competitive therapy for RRMM."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

GPRC5D CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first-in-human, single-centre, single-arm, phase 1 trial. (PubMed, Lancet Haematol) - P1 | "The results of this study suggest that GPRC5D is an active target for immunotherapy in multiple myeloma. GPRC5D-targeted CAR T-cell therapy is a promising treatment modality for patients with relapsed or refractory multiple myeloma and deserves further testing."

CAR T-Cell Therapy • IO biomarker • Journal • P1 data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Leukopenia • Multiple Myeloma • Neutropenia • Novel Coronavirus Disease • Oncology • Thrombocytopenia • GPRC5D

Oricell Closes $45M Series B1 Financing to Expand Development of Key Products (PRNewswire) - "Oricell Therapeutics Co., Ltd...announced the close of a $45M Series B1 investment round after the completion of a $125M Series B fund-raise in July 2022....Since the debut of Oricell's first key product Ori-C101 at the 2021 American Society of Clinical Oncology ('ASCO') Annual Meeting, the Company has been overcoming many difficulties and made unremitting efforts to achieve all the expected milestones....With this new funding, the Company is now well-positioned to expand its products to the U.S., specifically OriCAR-017, a GPRC5D CAR-T therapeutic that treats relapsed and refractory multiple myeloma, which is a product currently on the stage of IND enabling both in the US and China."

Financing • Hematological Malignancies • Multiple Myeloma • Oncology

Oricell Publishes Data from POLARIS Clinical Study Evaluating OriCAR-017 in the Treatment of RRMM in The Lancet Haematology (PRNewswire) - P1 | N=15 | POLARIS (NCT05016778) | "Oricell Therapeutics...announced publication of data from a clinical study evaluating the efficacy of OriCAR-017, an autologous GPRC5D-directed CAR-T cell therapy, in the treatment of relapsed/refractory multiple myeloma...in The Lancet Haematology....The study revealed an impressive 100% overall response rate, with 60% stringent complete response and 40% very good partial response. All patients (100%) achieved MRD negative (10-5/ml). Additionally, of the 5 patients who relapsed after BCMA CAR T-cell therapy, 2 achieved stringent complete response and 3 achieved very good partial response. At the date cut-off time, the mPFS (median progression-free survival) has not yet been reached; for the 2 patients who had disease progression, one with GPRC5D-positive while the other one with GPRC5D-negative."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

PHASE I OPEN-LABEL SINGLE ARM STUDY OF GPRC5D CAR-T CELLS (ORICAR-017) IN PATIENTS WITH RELAPTSED/REFRACTORY MULTIPLE MYELOMA (POLARIS) (EHA 2022) - P1 | "Patient received lymphodepleting chemotherapy with Fludarabine 30mg/m 2 daily and cyclophosphamide 300mg/m 2 daily for 3 days followed by a single infusion of OriCAR-017...All CRS cases were rapidly relieved after conventional CRS intervention, including tocilizumab and steroids...100% ORR and 100% MRD negative rate, along with favorable safety evidenced support OriCAR-017 could be a competitive therapy for pts with R/RMM. Furthermore, pts who had relapsed from BCMA CAR-T therapy may still benefit from OriCAR-017 treatment."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Plasmacytoma

POLARIS: A Study of CAR-T Cells Targeting GPRC5D in the Treatment of r/r Multiple Myeloma (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Zhejiang University | Recruiting ➔ Active, not recruiting

CAR T-Cell Therapy • Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology • GPRC5D

Safety and Efficacy of Anti-BCMA/GPRC5D CAR-T Cell Therapy in Treating Relapsed and Refractory Multiple Myeloma(rr/MM) (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Xuzhou Medical University

CAR T-Cell Therapy • New P2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

OriCell Reports OriCAR-017 Phase I POLARIS study Data in Oral Presentation at American Society of Clinical Oncology(ASCO) Annual Meeting 2022 (PRNewswire) - P1 | N=NA | "OriCell Therapeutics Co., Ltd...reported the positive results from Phase I POLARIS study, an investigator-sponsored study evaluating Ori-CAR017, an autologous GPRC5D-directed CAR-T cell, in patients with relapsed/refractory multiple myeloma at American Society of Clinical Oncology (ASCO) annual meeting. Single Infusion of OriCAR-017 Demonstrates an Early, Deep and Durable Responses at All Dose Levels in Heavily Pretreated RRMM Patients, including Patients Who Relapsed from BCMA CAR-T Therapy. Overall Response Rate(ORR) was 100% with Complete Response (CR)/ stringent Complete Response (sCR) rate of 60%, including Five patients with prior BCMA CART therapy achieved 2 sCR, 2 VGPR and 1PR. Patient medium follow up time 175 days (range 35-281). All patients were progression free without additional therapy at data cutoff....'Next step, we will be focusing on filling an IND with the NMPA and FDA for Ori-CAR017.'"

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology