Ten Trispecific Antibody Innovations Received First-in-China IND Approvals in 2024 from Pfizer, Innovent, Qilu Pharma and Others
Johnson & Johnson
Medical Device R&D and Manufacturer
▎WuXi AppTec Content Team Report
On November 7, VibeBio reached a deal worth over $600 million for LBL-051, a preclinical CD19xBCMAxCD3 trispecific antibody new drug.Cooperation; and a few days ago, Chimagen Biosciences also reached an agreement with GlaxoSmithKline (GSK) regarding the CD3/CD19/CD20 T cell Engager trispecific antibody under research.Authorized Cooperation. These advances have once again drawn the industry's attention to tri-specific antibodies as a new type of drug.
According to a subsidiary journal of NatureNature Reviews Drug DiscoveryPreviously publishedReview ArticleIntroduction,Trispecific antibodies are also considered a new generation of bispecific antibody (bsAbs) technology format, aimed at overcoming the limitations of existing bsAbs therapies.Compared with bsAbs, trispecific antibodies can bind to three targets, often inducing deeper disease remission or offering better safety.
Since the beginning of this year, the research and development of trispecific antibody new drugs has also been making continuous progress.According to the official website of the Center for Drug Evaluation (CDE) under China's National Medical Products Administration and publicly available information, since 2024, at least 10 novel triple-specific antibody drugs have been approved for IND in China for the first time, entering the clinical research stage.These new drugs are intended to be developed for the treatment of malignant solid tumors, hematological malignancies, and autoimmune diseases.This article will introduce these three novel Class 1 anti-drugs.
Zhejiang Borui Biopharmaceutical Co., Ltd., Chimagen Biosciences：BR115
Mechanism of Action: Tri-specific Antibody Targeting HER2
Indications: Advanced Solid Tumors
In January 2024, Zhejiang Borui Biopharmaceutical Co., Ltd. and Chimagen Biosciences jointly developedClass 1 New DrugBR115（CMG6A19）InjectionApproved for Clinical Use`, Intended to develop treatment`Advanced Malignant Solid Tumors。According to the press release from Zhejiang Borui Biopharmaceutical Co., Ltd., BR115 was developed based on Chimagen Biosciences' innovative tri-specific antibody technology and can specifically bind toHER2 ECD2And/OrHER2 ECD4, and simultaneously with the T cell surfaceCD3Molecular binding recruits T cells near the target cells, redirects their cytotoxic effects, induces T-cell activation, and lyses target cells. Additionally, BR115 can dual-block HER2 downstream signaling to inhibit tumor cell growth.
Compared with traditional bispecific antibody drugs, BR115 canSelective killing of HER2-overexpressing tumor cells, while significantly reducing the effect on tissues with normal HER2 expression, demonstrates better tumor specificity and safety.; It has a preventive effect on tumor escape and recurrence caused by HER2 antigen mutations. Currently, BR115 injection is undergoing a Phase 1 clinical study for monotherapy in patients with advanced malignant solid tumors.
Johnson & Johnson:JNJ-80948543 Injection
Mechanism of Action: CD79b/CD20/CD3 Trispecific T Cell Redirecting Antibody
Indications: Malignant Lymphoma
In March 2024, Johnson & Johnson's Class 1 new drug JNJ-80948543 injection in ChinaApproved for Clinical Use, Intended to Develop Treatment forMalignant Lymphoma. Public information shows that this is aNovelCD79b/CD20/CD3 TrispecificT Cell RedirectionAntibody，ItCan bind to the CD3 antigen on T cells and CD79b and CD20 on B cells, leading to the lysis of malignant B cells.。
According to the public information released by Johnson & Johnson,Compared with bispecific antibodies,TheTrispecific antibodies canEnhanced affinity to increase potency and maximize tumor eradication in the presence of non-target cell populations, thereby improving therapeutic efficacy.At present, the product is undergoing Phase 1 clinical trials internationally (including in China) for the treatment of chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma across various hematological malignancies.
Simcere Zaiming: Injectable SIM0500
Mechanism of Action: GPRC5D/BCMA/CD3 Trispecific Antibody
Indications: Multiple Myeloma
In March 2024, Simcere Zaiming's Class 1 new drug, SIM0500 for injection, was approved for clinical trials, intended for the treatment of adult patients with relapsed or refractory multiple myeloma. According to publicly available information from Simcere Zaiming, this is aHumanized GPRC5D-BCMA-CD3 Trispecific AntibodyDeveloped through Simcere's proprietary T-cell engager multispecific antibody technology platform.It forms a specific tumor-targeting T-cell activating drug through a low-affinity, high-target-activated CD3 antibody combined with anti-tumor-associated antibodies, leveraging the synergistic effects of multiple antibody actions.. The product is currently undergoing clinical development simultaneously in China and the United States, and has already been granted by the U.S. FDAFast Track Designation, for the indication of multiple myeloma that has previously received ≥3 lines of therapy.
Pfizer:PF-07264660 Injection,PF-07275315 Injection
Mechanism of Action: Anti-IL-4/IL-13/IL-33 Tri-specific Antibody, Anti-IL-4/IL-13/TSLP Tri-specific Antibody
Indications: Atopic Dermatitis
In June 2024, Pfizer's two novel Class 1 tri-specific antibody drugs in ChinaApproved for Clinical Use, all intended for the development of treatmentsModerate to Severe Atopic Dermatitis in AdultsAccording to public information from Pfizer, these two products are new molecular entities in the company's inflammation and immunology pipeline. PF-07264660 isAnti-IL-4/IL-13/IL-33 Trispecific Antibody, PF-07275315 isAnti-IL-4/IL-13/TSLP trispecific antibody.These two trispecific antibodiesWhile more effectively blocking the IL-4/IL-13 signaling pathway, it canBy inhibiting TSLP to produce broader effects, or by further suppressing itching through the inhibition of the IL-33 pathway, which is expected to produce better efficacy in the treatment of atopic dermatitis.
Currently, Pfizer is conducting a Phase 2 international multicenter clinical trial (including China) to evaluate the efficacy and safety of PF-07275315 and PF-07264660 in adult participants with moderate to severe atopic dermatitis.
Qilu Pharmaceutical: QLS4131 for Injection
Mechanism of Action: Tri-specific Antibody
Indications:Multiple Myeloma
Innovent Biologics: IBI3003
Mechanism of Action: GPRC5D/BCMA/CD3 Tri-specific Antibody
Indications: Multiple Myeloma
July 2024,Innovent Biologics' Class 1 New Drug IBI3003 Approved for Clinical Trials, Intended for TreatmentPatients with relapsed or refractory multiple myeloma. According to the public information from Innovent Biologics, this is aGPRC5D/BCMA/CD3 Tri-specific Antibody ProductCurrently, Innovent Biologics is conducting a Phase 1/2, international multicenter, open-label, first-in-human study of IBI3003 in subjects with relapsed or refractory multiple myeloma.
SCTB41 Injection by Sinocelltech
Mechanism of Action: Tri-specific Antibody Products
Indications: Advanced malignant solid tumors
In August 2024, Sinocelltech's Class 1 new drug SCTB41 Injection was approved for clinical trials, intended for the treatment ofAdvanced Malignant Solid TumorsAccording to the announcement by Shenzhou Cell, SCTB41 is a product independently developed by the company with the goal of achieving differentiated advantages.Trispecific Antibody Injection for Immunotherapy of Multiple Solid Tumors. This clinical approval is intended for monotherapy to treat advanced malignant solid tumors. SinoCellTech is currently conducting a Phase 1/2 clinical trial to evaluate SCTB41 for the treatment of patients with advanced malignant solid tumors.
Huiyu Pharmaceutical: Injectable HY07121
Mechanism of Action: Tri-target Antibody Fusion Protein Targeting PD-1/TIGIT/IL-15
Indications: Advanced Solid Tumors
September 2024, Huiyu PharmaceuticalWholly-owned subsidiaryHuiyu Haiyue Pharmaceutical's Class 1 new drug, HY07121 for injection, has been approved for clinical trials and is intended for patients with advanced solid tumors. According to Huiyu Pharmaceutical's announcement, this is aAnti-PD-1, Anti-TIGIT, IL-15/IL-15Rα Tri-target Antibody Fusion Protein. In vitro pharmacodynamic studies have shown that the multi-antibody molecule obtained through special designUnder equimolar conditions, the stimulation of human immune cytokine IFN-γ secretion levels shows superior potential compared to the combination of three targets.. This product has the mechanism of enhancing the efficacy of tumor immunotherapy and overcoming immune resistance. The product is currently undergoing Phase 1/2 studies for the treatment of advanced malignant solid tumors.
AstraZeneca:AZD5492
Mechanism of Action:CD20×TCR×CD8 Tri-specific Antibody
Indications: B-cell malignancies
October 2024, AstraZeneca(AstraZeneca)AZD5492 in ChinaApproved for Clinical Use, Intended forTreatment of Relapsed or Refractory B-Cell Malignancies. Public information shows that this is aCD20×TCR×CD8 Trispecific Antibody, is a CD8-guided T-cell engager. Preclinical studies have shown,Compared with traditional CD20xCD3 T cell engagers,AZD5492Able toBy preferentially engaging CD8+ T cells to induce a certain level of B cell killing, while reducing the activation of CD4+ T cells and associated cytokine production.Previously, AstraZeneca has conducted Phase 1/2 clinical trials of AZD5492 for the treatment of relapsed/refractory B-cell malignancies in countries such as the United States and Australia.
In addition to the aforementioned new drugs, BeiGene's research and development includesEGFR/MET Trispecific AntibodyBG-T187 Submitted IND in China this September, Novartis' Potential "First-in-Class"Anti-CD3/CD19/CD2 Trispecific AntibodyPIT565An IND application has also been submitted in China a few days ago, and it is expected to formally enter the clinical research stage in China soon. In addition,Several innovative trispecific antibody drugs have entered clinical trials in China, such as the CD19/CD3/CD28 trispecific antibody developed by Huihe Bio.CC312Lyophilized Powder for Injection, Zelgen Pharma CD3×DLL3×DLL3 Trispecific Antibody for InjectionZG006And so on, no more details will be listed here.
We hope that the subsequent clinical research of these drugs under development will proceed smoothly, and they can bring better treatment options to patients as soon as possible.
[2] Official websites of various companies and publicly available information
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