Innovent Biologics, Inc., a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, together with IASO Biotherapeutics (IASO Bio), jointly announced to deliver an oral presentation on updated data from the Phase I study of IBI326 in patients with relapsed/refractory multiple myeloma (R/R MM) at the European Hematology Association (EHA) Congress, June 9-17, 2021. The presentation will further demonstrate the safety, efficacy, and increased persistence of IBI326.

IBI326 is a fully-human B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy co-developed by IASO Bio and Innovent, and it is currently under the pivotal Phase II clinical trial. In February 2021, IBI326 was granted the Breakthrough Therapy Designation (BTD) by China regulatory authority, National Medical Production Administration (NMPA) for the treatment of relapsed/refractory multiple myeloma.

In the oral presentation, Professor Chunrui Li with Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology (HUST) in China will report the clinical data on 35 patients with R/R MM, who received 1.0, 3.0, or 6.0 × 106/kg IBI326 treatment respectively in the dose-escalation phase and dose-expansion cohort. The 1.0 × 106/kg dose was determined as Recommended Phase II Dose (RP2D). The median age of the 35 patients was 54 (27, 72). Among them, eight patients had extramedullary multiple myeloma (EMM) and one patient had complication with plasma cell leukemia. The median number of prior treatment regimens was four (3, 12). Ten patients previously received autologous hematopoietic stem cell transplantation (AHSCT), and 10 patients received murine BCMA CAR-T treatment. As of May 1, 2021, the median follow-up of the 35 patients was 291 days (21, 954).

• IBI326 has a rapid onset of action and long-lasting efficacy. The overall response rate (ORR) was 97.1% in the 35 patients, among whom 29 patients (82.9%) achieved ≥ VGPR and 20 patients (57.1%) achieved complete response/stringent complete response (CR/sCR). And 34 patients evaluable for MRD achieved minimal residual disease (MRD) negativity, with the median time to MRD negativity 1.3 (0.7, 4.1) months.

• All patients previously treated with murine BCMA CAR-T or patients with extramedullary multiple myeloma (EMM) benefited from IBI326. Among all 35 patients, eight were with EMM, among whom eight (75%) achieved ≥VGPR, two (25%) achieved PR, eight patients achieved ≥PR. Among all 35 patients, 10 patients were treated with a prior murine BCMA CAR-T treatment, among whom eight (80%) achieved ≥VGPR, one (10%) achieved PR, one（10%）achieved stable disease (SD).

• IBI326 has a good safety profile. Five of the 35 patients had cytokine release syndromes (CRS) of Grade 3 or above. The median time to onset of CRS was 4 (1, 9) days, and all CRS could be efficiently controlled by tocilizumab and/or steroids. ICANS was observed in only one patient whose symptom was drowsiness; the patient later spontaneously relieved without any treatment.

• IBI326 was persistent in the patients. The median time to reach the peak of IBI326 expansion in the patients was 12 (7, 17) days. As of the cut-off date, three patients had IBI326 persistence for over two years, and the first patient of them achieved persistent sCR.

• IBI326 has lower immunogenicity. Only two patients (5.7%) were detected positive for anti-drug antibody (ADA), and the immunogenicity was significantly lower than that of the prior murine BCMA CAR-T treatment.

The clinical data of the study in patients with R/R MM presented at the 61st American Society of Hematology (ASH) Annual Meeting in 2019 highlighted the impressive safety profile, efficacy, and durability of response of IBI326. The study also included four patients who had relapsed after prior murine BCMA CAR T-cell treatment. The overall response of these four patients demonstrated that IBI326 can also be an effective treatment option for patients who have relapsed from a prior CAR-T therapy.

In June 2021, the results were published in Blood, a peer-reviewed journal specializing in hematology, in an article titled "A phase 1 Study of a Novel Fully Human BCMA-targeting CAR (IBI326) in Patients with Relapsed/Refractory Multiple Myeloma." The editors of Blood were impressed by the unique persistence of IBI326 and the authors' exposition on the re-treatment prospects of the disease during the study. Therefore, they invited experts from University College London Cancer Institute to write a review titled "BCMA CARs in multiple myeloma: room for more?" (DOI 10.1182/blood.2021010833).

Dr. Hui Zhou, Senior Vice President of Medical Development, Innovent Biologics, said, "We are glad to see that the excellent clinical data of IBI326 (IASO: CT103aA) has been highly recognized by the EHA congress. In particular, it still shows good clinical benefits to the patients who received prior murine BACM CAR-T treatment, and provides better treatment options for patients with relapsed/refractory multiple myeloma. We look forward to the launch of this cell therapy to benefit patients in the future. "

Maxwell Wang, Chief Executive Officer of IASO Bio, said, "We are very glad that our high-quality clinical data are presented at the European Hematology Association Congress, one of the top global academic conferences. It's also the only oral presentation on a China-developed BCMA CAR-T treatment at this year's EHA Congress. The updated data reinforce the advantages and uniqueness of CT103A in the treatment of patients with relapsed/refractory multiple myeloma. Particularly, we enrolled 8 patients with extramedullary multiple myeloma and 10 patients receiving prior murine BCMA CAR-T treatment. All patients have obtained clinical benefits. IASO Biotherapeutics will continue to leverage its innovative clinical development strategy to further prove the advantages of CT103A. We also look forward to the oral presentation by Professor Chunrui Li with Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology (HUST) at the EHA Congress."

About Multiple Myeloma

Multiple Myeloma is a deadly blood cancer that often infiltrates the bone marrow causing anemia, kidney failure, immune problems, and bone fractures. For multiple myeloma patients, common first-line drug treatments include proteasome inhibitors, immunomodulatory drugs, and alkylating agents. While treatment may result in remission, most patients will inevitably enter the relapsed or refractory stage as there's currently no cure. As a result, there is a significant unmet need for patients with relapsed/refractory multiple myeloma.

About IBI326 (BCMA CAR-T)

IBI326 is an innovative therapy co-developed by Innovent and IASO Bio. Previous studies indicate subjects with relapsed/refractory multiple myeloma (R/R MM) who received high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re-infusion of CAR-T cells will not be effective. To solve this dilemma, IBI326 has been developed, a lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3ζ activation domains. Based on strict selection and screening, utilizing a proprietary in-house optimization platform, the construct of the BCMA CAR-T is potent and persistent. In February 2021, IBI326 was granted breakthrough therapy designation by the NMPA for the treatment of relapsed/refractory multiple myeloma.

About Innovent 

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high quality innovative medicines for the treatment of cancer, autoimmune, metabolic diseases, and other major therapeutic areas. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong, S.A.R., China Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. By leveraging this platform, the company has built a robust pipeline of 24 valuable assets in major therapeutic areas, with 4 products officially approved for marketing in China - TYVYT? (sintilimab injection), BYVASDA? (bevacizumab biosimilar injection), SULINNO? (adalimumab biosimilar injection) and HALPRYZA? (rituximab biosimilar injection), one Biologics License Application (BLA) submission for sintilimab accepted by the U.S. FDA, six assets in Phase 3 or pivotal clinical trials, and 14 more molecules in clinical trials. TYVYT? (sintilimab injection) was included in the National Reimbursement Drug List (NRDL) in 2019 as the historically first PD-1 inhibitor entering in NRDL and the only PD-1 included in the list in that year.

Innovent has built an international team of advanced talented professionals in high-end biopharmaceutical development and commercialization, including many overseas experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with all relevant parties to help advance China's biopharmaceutical industry, improve drug availability to ordinary people and enhance the quality of the patients' lives. 

About IASO Bio

IASO Bio is a clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and autoimmune diseases. Leveraging its proprietary fully human antibody discovery platform (IMARS), high-throughput CAR-T drug priority platform, and proprietary manufacturing processes, IASO Bio is developing a rich clinical-stage pipeline of multiple autologous and allogeneic CAR-T and biologics product candidates. Currently, the company is developing a diversified portfolio of over 10 novel pipeline products, IASO's leading asset, IBI326, an innovative anti-BCMA CAR-T cell therapy under pivotal study for relapsed/refractory (R/R) multiple myeloma (RRMM), was granted Breakthrough Therapeutic Designation by China's National Medical Products Administration (NMPA) in February 2021.