Long-term Follow-up Data of Equecabtagene Autoleucel (CT103A/IBI326), a Fully Human Anti-BCMA CAR-T Therapy, in Relapsed/Refractory Multiple Myeloma: Updated Results from the Phase 1/2 FUMANBA-1 Trial Presented at ASCO 2023

Nanjing, Shanghai, and San Jose, CaliforniaJune 6, 2023/PR Newswire/ -- IASO Bio, a clinical-stage biopharmaceutical company dedicated to the development of innovative cell therapies, and Innovent Biologics Group (abbreviated as "Innovent Bio") (Hong Kong Stock Exchange stock code: 01801), a biopharmaceutical company dedicated to the research, development, production, and commercialization of innovative medicines in major disease areas including oncology, autoimmunity, metabolism, and ophthalmology,jointly announced atAt the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, the latest results from the Phase 1/2 registration clinical study of the co-developed fully human autologous B-cell maturation antigen (BCMA) chimeric antigen receptor autologous T-cell (CAR-T) therapy (equecabtagene autoleucel injection, development code: CT103A by IASO Bio, IBI326 by Innovent Bio) were presented as a poster (Abstract No.: 8025).

Founded in 1964, the American Society of Clinical Oncology (ASCO) plays a pivotal role in the global clinical oncology community due to its profound influence and authority, and is widely recognized as the most important oncology academic conference worldwide. The annual ASCO Annual Meeting draws leading cancer experts and research teams from across the globe to Chicago, where numerous cutting-edge and highly anticipated research findings and clinical data are selected for their first presentation.

Abstract Title:Long-Term Follow-Up Data Update from a Phase 1/2 Clinical Study of Fully Human BCMA-Specific CAR-T Cells (CT103A) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) (FUMANBA-1)
Abstract Number:ASCO-8025
Meeting Theme:Hematologic Malignancies: Plasma Cell Disorders
Meeting Time: June 5, 2023 (Monday) 8:00-11:00CDT
Conference Venue:United States — Chicago (Online + Offline)
Report Format:Poster Presentation

This report presents updated safety and efficacy data from the Phase 1/2 registration clinical study (FUMANBA-1) of Equecabtagene Autoleucel Injection for the treatment of relapsed/refractory multiple myeloma (hereinafter referred to as "RRMM") at 14 clinical research centers in China.

This study (ChiCTR1800018137, NCT05066646) enrolled patients with relapsed/refractory multiple myeloma (RRMM) who had previously received at least three lines of therapy (including regimens containing proteasome inhibitors and immunomodulatory drugs) and experienced disease progression after their last line of treatment. As of September 9, 2022, a total of 103 subjects who received an infusion of equecabtagene autoleucel injection were included, at an infusion dose of 1.0×10⁶CAR-T cells/kg, with a median follow-up time of 13.8 (0.4, 27.2) months and a median of 4 (3–23) prior lines of therapy.

Among the 103 subjects who received equecabtagene autoleucel infusion, 68.9% (71/103) had high-risk cytogenetic abnormalities per mSMART 3.0 criteria, 12.6% (13/103) had extramedullary plasmacytoma, and 11.7% (12/103) had previously received non-fully humanized BCMA CAR-T therapy.

Equecabtagene autoleucel injection demonstrates progressively deepening and durable efficacy:Among the 101 efficacy-evaluable subjects, the overall response rate (ORR) was 96.0% (97/101). Of these, 91.1% (92/101) achieved a very good partial response or better (≥VGPR), and the stringent complete response/complete response (sCR/CR) rate was 74.3% (75/101). The median time to response was 16 (11, 179) days. The median duration of response (DOR) and median progression-free survival (PFS) were not reached, with a 12-month PFS rate of 78.8% (95% CI: 68.6–85.97). Minimal residual disease (MRD) negativity was achieved in 95.0% (96/101) of subjects, with all sCR/CR subjects achieving MRD negativity. Furthermore, 82.4% (95% CI: 70.90–89.72) of subjects maintained MRD negativity for over 12 months, and the median duration of MRD negativity was not reached.

Equecabtagene autoleucel injection also demonstrated favorable efficacy in subjects with multiple myeloma (hereinafter referred to as "MM") who had previously received CAR-T therapy. Among 12 MM subjects with prior CAR-T therapy, 9 achieved CR, 5 achieved sCR, of whom 4 maintained sCR for over 18 months.

Equecabtagene autoleucel injection demonstrates an excellent and manageable safety profile:Among 103 subjects, 93.2% (96/103) experienced cytokine release syndrome (CRS), predominantly Grade 1–2, with only one subject developing Grade ≥3 CRS. The median time to onset of CRS was 6.0 days (range: 1–13) post-infusion, and the median duration was 5.0 days (range: 2–30). Only 2.5% (2/79) of subjects developed immune effector cell-associated neurotoxicity syndrome (ICANS), with one case each of Grade 1 and Grade 2. All CRS and ICANS events resolved. The most common drug-related adverse events were hematologic toxicities.

Iqir-? injection demonstrates robust expansion and durable persistence in vivo:The median time to peak CAR copy number in peripheral blood was 12 days post-infusion, with a median peak level of 87,570.6 copies/μg DNA. Among subjects followed up to 12 and 24 months post-infusion, CAR-T cell persistence remained detectable in 50% (28/56) and 40% (4/10) of subjects, respectively. Only 19.4% (20/103) of subjects tested positive for anti-drug antibodies (ADA) following infusion.

Professor Qiu Lugui from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Professor Li Chunrui from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, the principal investigators of this clinical study, stated: "Multiple myeloma is the second most common hematological malignancy. Current mainstay therapeutic agents include proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs). Although the treatment of multiple myeloma has significantly improved over the past two decades, it remains an incurable disease. Equecabtagene autoleucel is a BCMA-targeted CAR-T cell therapy. Its CAR construct incorporates fully human single-chain variable fragments (scFvs), which confer low immunogenicity in the host and reduce the likelihood of inducing anti-CAR antibodies, while preserving anti-tumor activity."

At the current ASCO Annual Meeting, we presented updated efficacy and safety results of equecabtagene autoleucel injection in patients with relapsed/refractory multiple myeloma (RRMM) based on a longer follow-up period. Compared with the clinical data from 79 subjects reported at the 2022 EHA Congress, the number of subjects in this update increased to 103, and the median follow-up time was extended from 9.0 months to 13.8 months, demonstrating superior efficacy of equecabtagene autoleucel injection (sCR/CR rate increased from 68.4% to 74.3%). We are particularly encouraged by the finding that among BCMA CAR-T–naïve subjects with a follow-up duration of at least 12 months, the sCR/CR rate reached 87.3%. Looking ahead, with breakthrough advancements in CAR-T cell therapy, the clinical development of CAR-T products is expected to expand into first- and second-line treatment settings, and we look forward to these therapies benefiting a wider population of cancer patients."

# About Multiple Myeloma

Multiple myeloma (MM) is one of the most common hematologic malignancies, characterized as a malignant disease driven by the aberrant proliferation of clonal plasma cells. For newly diagnosed MM patients, commonly used first-line therapies include proteasome inhibitors, immunomodulatory drugs, and alkylating agents. For the majority of patients, standard first-line treatment can maintain disease stability for 3 to 5 years; however, a small subset exhibits primary resistance upon initial treatment, resulting in inadequate disease control. Even among the majority of initially responsive patients, the disease inevitably progresses to a relapsed/refractory stage following the period of stability. Therefore, significant unmet medical needs remain for patients with relapsed/refractory multiple myeloma (RRMM).

In the United States, MM accounts for nearly 2% of all cancer patients and over 2% of cancer-related deaths. According to a Frost & Sullivan report: In China, the annual number of new MM cases increased from 18,900 in 2016 to 21,100 in 2020, and is expected to reach 24,500 by 2025. The number of prevalent MM cases in China increased from 69,800 in 2016 to 113,800 in 2020, and is projected to reach 182,200 by 2025; in the United States, the annual number of new MM cases increased from 30,300 in 2016 to 32,300 in 2020, and is expected to reach 37,800 by 2025. The number of prevalent MM cases in the United States increased from 132,200 in 2016 to 144,900 in 2020, and is projected to reach 162,300 by 2025.

About Icilocabtagene Autoleucel Injection

IASO Bio and Innovent Bio are collaborating on the clinical development in China of equecabtagene autoleucel injection for relapsed and refractory multiple myeloma (RRMM). This candidate product is a CAR-T cell therapy targeting B-cell maturation antigen (BCMA), utilizing a lentiviral vector to transduce autologous T cells. The CAR construct comprises a fully human single-chain variable fragment (scFv), a CD8α hinge and transmembrane domain, a 4-1BB co-stimulatory domain, and a CD3ζ activation domain. Based on rigorous screening and comprehensive in vitro and in vivo functional evaluations, equecabtagene autoleucel injection demonstrates potent and rapid efficacy, along with remarkable in vivo persistence.

Previously, equecabtagene autoleucel injection successively received the "Breakthrough Therapy Designation (BTD)" from the NMPA and the "Orphan Drug Designation (ODD)" from the FDA for the treatment of RRMM. In June 2022, the New Drug Application (NDA) for equecabtagene autoleucel injection for the treatment of RRMM was officially accepted by the National Medical Products Administration (NMPA). In the same year, it received FDA approval to initiate clinical trials. In February 2023, equecabtagene autoleucel injection was further granted the Regenerative Medicine Advanced Therapy (RMAT) designation and Fast Track (FT) designation by the FDA. Beyond MM, the Investigational New Drug (IND) application for equecabtagene autoleucel injection for a newly expanded indication—antibody-mediated neuromyelitis optica spectrum disorder (NMOSD)—has been approved by the NMPA.