IASO Bio and Innovent Announce Updated Phase 1/2 Clinical Data of IBI326 (CT103A), a Fully Human BCMA-Targeted CAR-T Therapy, in Oral Presentation at ASH Annual Meeting

On December 13, IASO Bio and Innovent Bio (Stock Code: 01801.HK) jointly announced that the latest Phase 1/2 registrational clinical study results of their co-developed fully human autologous B-cell Maturation Antigen (BCMA)-targeted Chimeric Antigen Receptor Autologous T-cell (CAR-T) therapy (IASO Bio's R&D code: CT103A; Innovent Bio’s R&D code: IBI326) were presented as an oral report at the 63rd American Society of Hematology (ASH) Annual Meeting in 2021. The title of the oral presentation was: A Phase 1/2 Clinical Study of Fully Human B-Cell Maturation Antigen-Specific CAR-T Cells (CT103A) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) (Abstract No.: 547). The presenter was Professor Chunrui Li from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

The study presented in the ASH oral report is a single-arm, open-label, multi-center clinical trial currently being conducted in China. The study primarily enrolled RRMM patients who had received ≥ 3 prior lines of therapy, were positive for BCMA expression on plasma cell membranes, and had an ECOG score of 0-1. The primary endpoint was overall response rate (ORR), with secondary endpoints including duration of response (DOR), progression-free survival (PFS), overall survival (OS), as well as safety and tolerability, pharmacokinetic, and pharmacodynamic profiles. The clinical data cutoff date reported at this meeting was October 12, 2021, with a total of 79 subjects receiving the Phase II recommended dose (RP2D) of 1.0×106 CAR-T/kg (including 9 subjects participating in investigator-initiated early exploratory studies [IIT] and 70 subjects participating in the registrational clinical study [NCT05066646]).

The study results showed that CT103A has excellent safety and efficacy in humans and a long-lasting persistence in the body, and is expected to become a breakthrough treatment for patients with relapsed or refractory multiple myeloma.

CT103A Demonstrates Excellent and Controllable Safety: Among 79 subjects, 75 (94.9%) experienced cytokine release syndrome (CRS), the majority being Grade 1-2 CRS, with only 2 subjects experiencing Grade 3 CRS (both occurred during the IIT study phase; no Grade 3 or higher CRS was observed among the 70 subjects in the registered clinical phase). The median time of CRS onset was Day 6.0 post-infusion, and the median duration of CRS was 5.0 days. Only one subject developed Grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS), characterized by transient decreased consciousness, which resolved spontaneously. All subjects' CRS and ICANS were resolved, with 20% of subjects treated with tocilizumab and 34.7% treated with corticosteroids.

CT103A Demonstrates Outstanding and Durable Efficacy: Among 79 subjects, the ORR was 94.9%, with a complete response/stringent complete response (CR/sCR) rate of 58.2%. Responses deepened over time with extended follow-up. The PFS rates at 6 months, 9 months, and 12 months post-infusion were 78.0%, 76.0%, and 71.0%, respectively. CT103A also showed favorable efficacy in subjects with extramedullary multiple myeloma, with an ORR of 100% and CR/sCR of 72.7% among 11 subjects with extramedullary disease. Among the 79 subjects, 93.7% achieved minimal residual disease (MRD) negativity at a sensitivity of 10-5 at least once after infusion.

CT103A Demonstrates Good Efficacy in Subjects Relapsed After Prior CAR-T Therapy: In 13 subjects who received prior CAR-T therapy, the ORR was 76.9%, with 61.5% achieving very good partial response (VGPR) or better, and CR/sCR at 46.2%.

CT103A Demonstrates Robust Expansion and Persistent Survival In Vivo. The median time to peak CAR copy number of CT103A in peripheral blood was 12 days, with a median peak of 92,000 copies/μg DNA. Among 18 subjects followed up for 12 months post-infusion, 10 (55.6%) still had detectable levels of CT103A. The first subject treated maintained detectable levels of CT103A in peripheral blood at 34 months (1,013 days) post-infusion (4,040 copies/μg DNA) and remained in sCR status. Following CT103A infusion, free BCMA in peripheral blood rapidly decreased and remained below the limit of detection for an extended period.

CT103A Demonstrates Low Immunogenicity: Only 1.3% (1/79) of subjects tested positive for ADA within 3 months after CT103A infusion. With a median follow-up of 7 months, only 12.7% (10/79) tested positive for ADA.

The group leader unit of this research project, Professor Qiu Lugui from the Blood Disease Hospital of the Chinese Academy of Medical Sciences and Professor Li Chunrong from Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology, both stated:

"Although previous BCMA-targeted CAR-T therapies have shown good efficacy in RRMM, the high relapse rate remains a challenge to be addressed. CT103A is a fully human, BCMA-targeted CAR-T product that can reduce potential anti-CAR immunogenicity in hosts and decrease the risk of relapse. The study demonstrated CT103A's favorable efficacy, excellent safety, good kinetics, and low immunogenicity, which are of great significance for RRMM treatment and represent a breakthrough direction for future research."

Dr. Wang Wen, CEO and Chief Medical Officer of IASO Bio, stated: "This is the second time that CT103A's clinical data has been presented as an oral report at the ASH Annual Meeting, with both efficacy and safety data being highly encouraging. This dataset includes partial results from a multi-center registrational clinical study involving 11 centers. Notably, this is the world’s first registrational clinical trial to enroll subjects who had previously failed CAR-T therapy, addressing an unmet medical need for which no treatment options exist. Despite this, CT103A continues to demonstrate robust and durable therapeutic effects, further showcasing the strength of this innovative product. Currently, the company is advancing CT103A’s clinical development across four dimensions: frontline treatment, combination therapies, indication expansion, and global outreach. The company is preparing to submit a New Drug Application (NDA) as soon as possible, hoping for the product’s swift market entry to save more patients’ lives."

Dr. Hui Zhou, Senior Vice President of Innovent Bio, stated: "Multiple myeloma is a common and highly prevalent malignant tumor in the blood system, and recurrence and drug resistance are inevitable during treatment. There is an urgent clinical need for treatments with good tolerability and deep, durable responses. We are very pleased that the Phase I/II clinical study results of CT103A (Innovent's R&D code: IBI326) were orally presented at this year’s ASH Annual Meeting, demonstrating the outstanding and sustained efficacy and excellent safety profile of IBI326. This also motivates us to further accelerate the clinical development and registration of IBI326, bringing new hope to patients with multiple myeloma."

About Multiple Myeloma (MM)

Multiple Myeloma (MM) is one of the most common blood cancers and is a malignant disease characterized by the abnormal proliferation of clonal plasma cells. For newly diagnosed multiple myeloma patients, commonly used first-line treatments include proteasome inhibitors, immunomodulatory drugs, and alkylating agents. For the majority of patients, these first-line treatments can stabilize the condition for 3-5 years, but a small number of patients exhibit primary resistance at initial treatment, and their condition cannot be effectively controlled. Most patients who initially respond to treatment will inevitably enter the relapsed or refractory stage after a period of disease stability. Therefore, there remains an unmet need for patients with relapsed/refractory multiple myeloma. In the United States, MM accounts for nearly 2% of all cancer cases and over 2% of cancer-related deaths. According to a Frost & Sullivan report:

The number of newly diagnosed MM patients in the United States increased from 30,300 in 2016 to 32,300 in 2020, and is expected to rise to 37,800 by 2025. The total number of MM patients in the United States grew from 132,200 in 2016 to 144,900 in 2020, and is projected to reach 162,300 by 2025.

The number of newly diagnosed MM patients in China increased from 18,900 in 2016 to 21,100 in 2020, and is expected to grow to 24,500 by 2025. The prevalence of MM in China increased from 69,800 in 2016 to 113,800 in 2020, and is projected to reach 182,200 by 2025.

About CT103A (BCMA CAR-T)

CT103A is an innovative product jointly developed by IASO Bio and INNOVENT BIO. This product uses lentivirus as a gene carrier to transfect autologous T cells, and its CAR includes a fully human scFv, CD8a hinge and transmembrane domain, 4-1BB co-stimulatory domain, and CD3ζ activation domain. Based on stringent screening and comprehensive in vivo and in vitro functional evaluations, the CT103A CAR-T product demonstrates potent and rapid efficacy, with remarkable persistence in vivo. In February 2021, CT103A received the "Breakthrough Therapy Designation" from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for the treatment of relapsed/refractory multiple myeloma. In addition to multiple myeloma, this product is also undergoing non-registration clinical studies for the rare disease neuromyelitis optica and has completed the Pre-IND phase.

About IASO Bio

IASO Bio is an innovative biopharmaceutical company focusing on the development and commercialization of cell therapies and antibody drugs. Established in 2017, the company has built an international management team with extensive experience in new drug discovery, clinical research, and commercialization. With a strong foundation in developing cell-based therapeutics and antibody drugs for hematological malignancies, IASO Bio has expanded its focus to solid tumors and autoimmune diseases. The company possesses a comprehensive, end-to-end platform encompassing early discovery, regulatory submission, clinical development, and commercial manufacturing. Its multiple technology platforms include a fully human antibody discovery platform, a high-throughput CAR-T drug screening platform, a universal CAR technology platform, a manufacturing technology platform, and a clinical translational research platform. Currently, the company has 10 pipeline products at various stages of development. Among them, CT103A (a fully human BCMA chimeric antigen receptor autologous T-cell injection) is in the late stage of clinical development and was granted "Breakthrough Therapy" designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in February 2021. Another self-developed innovative product, CT120 (a fully human dual-target CD19/CD22 CAR-T cell injection), has entered clinical trials for indications including relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) and relapsed/refractory acute B lymphoblastic leukemia (B-ALL) that are CD19/CD22 positive.

With a highly efficient management team, a rich product pipeline, unique innovation in R&D and business models, IASO Bio is committed to becoming an influential innovative pharmaceutical company in the industry. It aims to bring truly innovative drugs that address clinical pain points and possess market competitiveness to the clinical stage and eventually to the market, paving new treatment paths for patients and bringing new hope. For more information, please visit the company website: www.iasobio.com or LinkedIn page: IASO Biotherapeutics (驯鹿医疗).

About Innovent Bio

"Start with trust, achieve through action." Developing high-quality biologics that are affordable for the general public is the ideal and goal of Innovent Bio. Founded in 2011, Innovent Bio is committed to the development, production, and sales of innovative drugs for the treatment of major diseases such as cancer, autoimmune disorders, and metabolic conditions. On October 31, 2018, INNOVENT BIOLOGICS(SUZHOU)CO LTD was listed on the Main Board of the Hong Kong Stock Exchange, stock code: 01801.

Since its establishment, the company has stood out among many biopharmaceutical companies with its innovative achievements and internationalized operating model. It has built a product chain comprising 26 new drug varieties, covering multiple disease areas such as oncology, metabolic diseases, and autoimmune diseases. Among these, seven varieties have been selected for the national "Major New Drug Creation" program. The company has received approval for six products (Sintilimab Injection, trade name: Tyvyt®, English trademark: TYVYT®; Bevacizumab biosimilar, trade name: Byvasda®, English trademark: BYVASDA®; Adalimumab biosimilar, trade name: Sulino®, English trademark: SULINNO®; Rituximab biosimilar, trade name: Halpryza®, English trademark: HALPRYZA®; Pemigatinib oral inhibitor, trade name: Pemazyre®, English trademark: PEMAZYRE®; Olverembatinib tablets, trade name: Nulast®). The FDA has accepted the application for Sintilimab in the United States. Five varieties have entered Phase III or pivotal clinical trials, and another 15 products have entered clinical studies.

Innovent Bio has assembled a team of top-tier biopharmaceutical development and industrialization professionals with international advanced expertise, including many returned overseas experts. It has also established strategic partnerships with international collaborators such as Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, and Hanmi Pharmaceutical from South Korea. Innovent Bio hopes to work together with everyone to enhance the development level of China's biopharmaceutical industry to meet the public's need for accessible medication and their aspirations for health and well-being. For more information, please visit the company website: www.innoventbio.com or the company LinkedIn page at www.linkedin.com/company/innovent-biologics/.