ROCKVILLE, Md. and SUZHOU, China, June 6, 2023 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, and IASO Biotechnology ("IASO Bio"), a clinical-stage biopharmaceutical company engaged in discovering, developing, and manufacturing innovative cell therapies and antibody products, today jointly announced that the updated data from Phase 1b/2 study of Equecabtagene Autoleucel (Innovent R&D code: IBI326, IASO Bio R&D code: CT103A), a fully-human anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy for the treatment of relapsed and/or refractory multiple myeloma (RRMM), was presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on June 2-6, 2023.
Poster Presentation Overview
The updated data showed long-term follow-up efficacy and safety of the Phase 1b/2 study (FUMANBA-1) conducted in 14 centers in China.
This study enrolled RRMM patients who received ≥ 3 lines of prior therapies containing at least a proteasome inhibitor and an immunomodulatory agent and were refractory to their last line of treatment (ChiCTR1800018137, NCT05066646).
As of the data cutoff date of September 9th, 2022, a total of 103 patients received CT103A at 1.0×106 CAR-T cells/kg with the median follow-up of 13.8 months (range 0.4, 27.2) and median prior four lines of therapy (range 3,23).
Among the 103 patients, 68.9% (71/103) had high-risk cytogenetic abnormalities per mSMART 3.0, 12.6%（13/103）had extramedullary multiple myeloma (EMM), and 11.7%（12/103）had received prior CAR-T therapy.
Equecabtagene Autoleucel showed deepening and durable efficacy: Among the 101 evaluable patients, the overall response rate (ORR) was 96.0% (97/101), with 91.1% (92/101) of those patients achieving very good partial response (VGPR) or deeper responses, and the stringent complete response/ complete response (sCR/CR) rate was 74.3% (75/101). The median time to response(mTTR) was 16 days (range 11-179). The median duration of response (DOR) and median progression free survival (PFS) have not been reached. The 12-month PFS rate was 78.8% (95% CI: 68.6–85.97). 95.0% (96/101) of patients achieved minimal residual disease (MRD) negativity, and all CR/sCR patients achieved MRD negativity. 82.4% (95%CI: 70.90-89.72%) of patients achieved sustained MRD negativity over 12 months and the median duration of MRD negativity was not reached.
In 89 patients without prior CAR-T therapy, ORR was 98.9% (88/89), including 78.7% (70/89) of patients reaching CR/sCR. Of the 63 patients with ≥ 12 months follow-up (including patients that withdrew early), ORR was 98.4% (62/93）and 87.3%（55/63）reached sCR/CR. Of the 12 patients with prior CAR-T therapy, 75% (9/12) achieved response, and 5 patients achieved sCR (including 4 patients that sustained sCR for over 18 months post-infusion).
Equecabtagene Autoleucel demonstrated a favorable and manageable safety profile: Among the 103 patients, 93.2% (96/103) experienced cytokine release syndrome (CRS). The majority experienced grade 1~2 CRS, with only one experiencing ≥ grade 3 CRS. The median time to CRS onset was 6 days (range 1, 13) after infusion, and the median duration of CRS was 5 days (range 2, 30). Only two patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS), including one grade 1 and one grade 2 ICANS. All patients with CRS or ICANS have recovered. The most common ≥ grade 3 treatment-related AEs were still hematologic.
Equecabtagene Autoleucel demonstrated robust expansion and prolonged persistence and low immunogenicity: Equecabtagene Autoleucel in peripheral blood reached the peak at a median of 12 days post-infusion, with a median Cmax of 87570.6 copies/ug DNA. Equecabtagene Autoleucel was still detectable in 50% (28/56) and 40% (4/10) of the patients who completed 12-month and 24-month follow-ups after infusion. Only 19.4% (20/103) of the subjects were anti-drug antibody (ADA)-positive after Equecabtagene Autoleucel infusion.
"Multiple myeloma (MM) is the second most prevalent hematological malignancy. While current major drug therapies such as proteasome inhibitors (PIs), immunomodulators (IMiDs) and monoclonal antibodies (mAbs) have significantly improved MM treatments in the past two decades, it is still an incurable disease. The updated data from our ongoing clinical study of Equecabtagene Autoleucel presented at ASCO demonstrated that treatment with our a BCMA-targeted CAR-T therapy was effective and well-tolerated for a longer period of time,"said principal investigators 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." In comparison to the clinical data released at the EHA 2022 Congress, we're excited that our updated study data show that with the number of subjects receiving Equecabtagene Autoleucel increasing from 79 to 103, and the median follow-up time from 9.0 months to 13.8 months, Equecabtagene Autoleucel's efficacy further improved: the sCR/CR rate increased from 68.4% to 74.3%. It is more worth mentioning that the sCR/CR rate reached 87.3% in the subjects naïve to BCMA-targeted CAR-T therapies and followed up for at least 12 months. These results are encouraging and entails an opportunity to advance Equecabtagene Autoleucel to earlier lines of treatment to benefit more MM patients."
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. Additionally, the total number of patients diagnosed with MM increased from 132,200 in 2016 to 144,900 in 2020 and is expected to rise to 162,300 by 2025. In China, the number of new MM cases 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 Equecabtagene Autoleucel
Equecabtagene Autoleucel is an innovative fully-human anti- BCMA CAR-T cell therapy which uses lentivirus as a gene vector to transfect autologous T cells. The CAR contains a fully-human scFv, CD8a hinge and transmembrane, and 4-1BB-mediated co-stimulation and CD3ζ activation domains. Based on rigorous screening and comprehensive in vivo and in vitro evaluation, Equecabtagene Autoleucel is proven to have potent and rapid anti-myeloma activity and outstanding safety, efficacy, and persistence results.
Equecabtagene Autoleucel received New Drug Application (NDA) acceptance from China's National Medical Products Administration (NMPA) for the treatment of RRMM and obtained the U.S. FDA IND approval. The company also received Breakthrough Therapy Designation (BTD) from the NMPA in February 2021 and Orphan Drug Designation (ODD) in February 2022 and Regenerative Medicine Advanced Therapy (RMAT) and Fast Track (FT) Designations in February 2023 from the FDA. In addition to multiple myeloma, NMPA has accepted its IND application for the new extended indication of Neuromyelitis Optica Spectrum Disorder (NMOSD). Innovent and IASO Bio are jointly developing Equecabtagene Autoleucel for the treatment of RRMM in mainland China.
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 disease, metabolic disorder 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 35 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 8 approved products on the market. These include: TYVYT® (sintilimab injection), BYVASDA® (bevacizumab injection), SULINNO® (adalimumab injection), HALPRYZA® (rituximab injection), Pemazyre® (pemigatinib oral inhibitor), olverembatinib(BCR ABL TKI), Cyramza® (ramucirumab) and Retsevmo® (selpercatinib). An additional 3 assets are under NMPA NDA review, 6 assets are in Phase III or pivotal clinical trials, and 18 more molecules are 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, Roche, Sanofi, Adimab, Incyte, MD Anderson Cancer Center 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.
Disclaimer: Innovent does not recommend any off-label usage.
Note:
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.
CYRAMZA® (ramucirumab, Eli Lilly). Cyramza® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.
Retsevmo® (selpercatinib, Eli Lilly). Retsevmo® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.
About IASO Biotechnology
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 chimeric antigen receptor T-cell (CAR-T) drug screening 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 pipeline includes a diversified portfolio of over 10 novel products, including IASO's leading asset, Equecabtagene Autoleucel (CT103A), a fully human BCMA CAR-T injection.
In addition to Equecabtagene Autoleucel, the company's pipeline includes the fully developed in-house human CD19/CD22 dual-targeted CAR-T cell therapy which has received two IND clearances for treating relapsed/refractory B-cell non-Hodgkin's lymphoma (r/r B-NHL) and relapsed/refractory acute B-lymphoblastic leukemia (r/r B-ALL). CD19/CD22 is currently in Phase I clinical trials for r/r B-NHL. It was also granted ODD by the FDA in October 2021. In the approximately 20 patients dosed to date in the investigator-initiated trial, there were no ICANS, or immune effector cell-associated neurotoxicity syndrome, of any grade observed in any patient, and a grade 3 cytokine release syndrome (CRS) rate of less than 5%, with the remainder of patients experiencing no CRS or less than grade 3.
Leveraging its strong management team, innovative product pipeline, integrated manufactural and clinical capabilities, IASO aims to deliver transformative, curable, and affordable therapies that fulfil unmet medical needs to patients in China and around the world. For more information, please visit www.iasobio.com or www.linkedin.com/company/iasobiotherapeutics.
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