Innovent Biologics, Inc. (“Innovent”) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, and IASO Biotherapeutics (“IASO Bio”), a clinical-stage biopharmaceutical company focused on discovering, developing, and manufacturing innovative medicines, today jointly announced the latest data from the phase 1/2 clinical study of a fully human B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy in an oral presentation at the 63rd American Society of Hematology (ASH) Annual Meeting (Abstract # 547). BCMA CAR-T therapy was co-developed by the two companies (IASO Bio: CT103A, Innovent: IBI326) for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). Presentation title: A Phase 1/2 Study of a Novel Fully Human B-Cell Maturation Antigen-Specific CAR T Cells (CT103A) in Patients with Relapsed and/or Refractory Multiple Myeloma with Professor Chunrui Li, MD, PhD, from Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology (HUST) in China as the oral presenter.
The updated data is based on a single-arm, open-label, multi-center phase 1/2 study being conducted in China. The study mainly enrolled patients with BCMA-positive RRMM who had an Eastern Cooperative Oncology Group (ECOG) performance score of 0-1 and received ≥3 lines of prior therapy. The study’s primary endpoint is objective response rate (ORR), with secondary endpoints including duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD). As the data cutoff date of Oct.12, 2021, this study included 79 subjects treated with the recommended Phase II dose (RP2D) of 1.0×106 CAR-T cells/kg (9 from the exploratory investigator-initiated trial [IIT] and 70 from the registrational study [Trial Registration# NCT05066646]).
Study results showed that IBI326 has excellent safety and efficacy profiles, as corroborated by long in vivo persistence, indicating that IBI326 has the potential to be a breakthrough therapy for patients with RRMM.
IBI326 demonstrated a favorable and manageable safety profile: Among the 79 patients, 75 (94.9%) experienced cytokine release syndrome (CRS). The majority of them experienced 1~2 CRS; only 2 experienced grade 3 CRS (all occurred during the IIT phase of the study, while the 70 patients in the registrational study did not report any grade 3 or higher CRS). The median time to CRS onset was 6.0 days after infusion, and the median duration of CRS was 5.0 days. Only 1 patient experienced grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) manifested as transient decrease in consciousness and soon resolved without intervention. All patients with CRS or ICANS have resolved, among which 20% and 34.7% were treated with tocilizumab and steroids respectively.
IBI326 showed favorable and durable efficacy: Of the 79 patients, the ORR was 94.9% and the complete response/stringent complete response (CR/sCR) rate was 58.2%, with a trend suggesting a correlation between deeper responses and longer follow-ups. PFS at 6, 9, and 12 months after infusion was 78.0%, 76.0%, and 71.0%, respectively. IBI326 also demonstrated favorable efficacy in 11 patients with EMM, achieving an ORR of 100% and a CR/sCR rate of 72.7%. In all 79 patients, 93.7% achieved minimal residual disease (MRD)-negativity with a sensitivity of 10-5 at least once after infusion.
IBI326 also demonstrated favorable efficacy in patients who had received prior CAR-T therapy: Among the 13 patients who previously received CAR-T therapy, the ORR was 76.9%, with 61.5% of those patients achieving very good partial response (VGPR) or deeper responses, and 46.2% achieved CR/sCR.
IBI326 demonstrated robust expansion and prolonged persistence: The expansion of IBI326 in peripheral blood reached the peak at a median of 12 days, with a median Cmax of 92,000 copies/ug DNA. IBI326 was still detectable in 10 (55.6%) of the 18 patients who completed 12-month follow-up after infusion. The first enrolled patient still had detectable IBI326 transgene (4,040 copies/ug DNA) 34 months (1,030 days) after infusion, and remained in sCR during this time. Soluble BCMA in peripheral blood of patients rapidly declined after IBI326 infusion and persistently remained below the detectable limit.
IBI326 has low immunogenicity: Only 1.3% (1/79) of patients were tested anti-drug antibody (ADA)-positive within three months after IBI326 infusion. At a median follow-up duration of seven months, only 12.7% (10/79) of patients tested ADA-positive.
“While a high rate of relapse remains a major clinical challenge in RRMM, BCMA-targeted CAR-T has thus far showed great promise in its treatment. IBI326 is a fully-human BCMA-specific CAR-T therapy that can reduce relapse by bypassing potential anti-CAR immunogenicity in the host. This IBI326 study demonstrated favorable efficacy, safety, PK/PD, and low immunogenicity, signifying enormous therapeutic value for the treatment of RRMM as potentially a clinical breakthrough,” said the two principal investigators at the primary centers of the study – Prof. Lugui Qiu, MD, from the Chinese Academy of Medical Science Hematology Hospital and Prof. Chunrui Li, MD, PhD, from Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology.
Dr. Wen (Maxwell) Wang, Chief Executive Officer and Chief Medical Officer of IASO Bio, said: “This is our second time reporting CT103A results during an oral session at ASH Meeting. And this year’s new data for safety and efficacy of CT103A is particularly exciting. It includes some of the results from the registrational study at 11 sites which is worth emphasizing since it’s globally the first registrational study that enrolled patients who had failed prior CAR-T treatment. For these patients, who have no approved treatment options, CT103A also demonstrated favorable and durable efficacy, once again highlighting the enormous therapeutic potential of this innovative candidate. At present, we are also advancing the clinical development of CT103A for early-line treatments in combination therapies and autoimmune diseases, while expanding the development program globally. We’ll submit the new drug application (NDA) soon and look forward to launching this cell therapy to benefit even more patients in the future. “
Dr. Hui Zhou, Senior Vice President of Innovent, said: “Multiple myeloma (MM) is a common hematology malignant disease with high incidence rate, and relapse and refractory are inevitable after current treatments. There’s an urgent unmet need requesting a treatment with well-tolerated and long persistence for patients. We are glad the results from the Phase I/II study of CT-103A (Innovent R&D code: IBI326) were announced in an oral presentation at this year’s ASH Annual Meeting. These results looks very promising as they have demonstrated favorable and durable efficacy and manageable efficacy of IBI326. We will further accelerate this clinical development of IBI326 to bring forth a treatment option that will bring new hope to patients with MM.”
About Multiple Myeloma (MM)
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. In the United States, MM accounts for nearly 2% of all cancer cases, and more than 2% of cancer-related deaths.
According to Frost & Sullivan, the number of new MM cases in the United States rose from 30,300 in 2016 to 32,300 in 2020 and is expected to increase to 37,800 by 2025. The total number of patients diagnosed with MM in the United States increased from 132,200 in 2016 to 144,900 in 2020 and is expected to rise to 162,300 by 2025.
The number of new MM cases in China rose from 18,900 in 2016 to 21,100 in 2020 and is expected to increase to 24,500 by 2025. The total number of patients diagnosed with MM in China increased from 69,800 in 2016 to 113,800 in 2020 and is expected to rise to 182,200 by 2025.
About IBI326 (BCMA CAR-T)
IBI326 (BCMA CAR-T) is an innovative therapy co-developed by IASO Bio and Innovent Biologics. Previous studies indicate subjects with relapsed/refractory multiple myeloma (RRMM) 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 and integrated in house manufacture process improvement, the construct of the BCMA CAR-T is potent and IBI326 shows prolonged persistency in patients. In February 2021, IBI326 was granted Breakthrough Therapy Designation (BTD) by China’s National Medical Products Administration (NMPA) for the treatment of RRMM.
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 and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong 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. Leveraging the platform, the company has built a robust pipeline of 26 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 6 products approved for marketing in China – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA®(rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor) and olverembatinib (BCR-ABL TKI), a Biologics License Application (BLA) for sintilimab accepted for review in the U.S., 5 assets in Phase 3 or pivotal clinical trials, and an additional 15 molecules in clinical studies.
Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global 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 many collaborators to help advance China’s biopharmaceutical industry, improve drug availability and enhance the quality of the patients’ lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.
TYVYT® (sintilimab injection) is not an approved product in the United States.
BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States.
TYVYT® (sintilimab injection, Innovent)
BYVASDA® (bevacizumab biosimilar injection, Innovent)
HALPRYZA® (rituximab biosimilar injection, Innovent)
SULINNO® (adalimumab biosimilar injection, Innovent)
Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.
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. This includes a diversified portfolio of 10 novel pipeline products, including IASO’s leading asset, CT103A, an innovative anti-BCMA CAR-T cell therapy under pivotal study for relapsed/refractory multiple myeloma (RRMM). CT103A received Breakthrough Therapeutic Designation by China’s National Medical Products Administration (NMPA) in February 2021. In addition, the company’s in-house developed fully human CD19/CD22 dual-targeted chimeric antigen receptor (CAR)-T cell therapy has entered phase I/II registrational clinical trial for the treatment of CD19/CD22-positive relapsed/refractory B-cell non-Hodgkin’s lymphoma (r/r B-NHL).It was also granted Orphan Drug Designation by the U.S. FDA in October 2021. For more information on IASO Bio, please visit www.iasobio.com and or LinkedIn.
1. This indication is still under clinical study, which hasn’t been approved in China.
2. Innovent does not recommend any off-label usage.
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