Bispecific antibody - Competitive landscape, 2023

This “Bispecific antibody - Competitive landscape, 2023” report provides comprehensive insights about 250+ companies and 300+ drugs in Bispecific antibody Competitive landscape. It covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

Geography Covered

• Global coverage

Bispecific antibody: Understanding

Bispecific antibody: Overview

Immunoglobulins (antibodies [Abs]) are major protein components of the adaptive immune system, directed against foreign compounds and infectious agents. The IgG molecule consists of two light and two heavy chains connected by disulfide bonds; IgG is a monomer with a molecular weight of 146-160 kDa. Antigen-binding centers of Abs are formed by hypervariable regions of heavy and light chains. In the classical point of view, the Ab molecule contains two identical antigen-binding sites (two HL fragments) and is monospecific and bivalent. Immunoglobulins are expressed as receptors of the cell membrane of B lymphocytes, as well as in the form of soluble molecules secreted by plasma cells. Soluble Abs can bind virtually any natural and artificial molecules (antigens) with high affinity and specificity. The ability of Abs to recognize and bind a broad spectrum of antigens is ensured by their extraordinary diversity, reaching 108-1010 different variants of antigen-binding centers. Bispecific immunoglobulins contain two different antigen-binding sites.

Bispecific antibodies have been developed in which one antigen-binding site is directed against the CD3 receptor (activates cytotoxic T lymphocytes) and the other against specific antigens of tumor cells (CD19, CD20, CD33, CD123, HER2, epithelial cell adhesion molecule [EpCAM], BCMA, CEA, and others). The convergence of cytotoxic T lymphocytes and tumor cells due to Bispecific antibody binding activates cytotoxic T cells and promotes the destruction of tumor cells. In addition to a wide range Bispecific antibodies directed against tumors, several bispecific molecules for the treatment of other diseases have been developed. The Bispecific antibody for the treatment of osteoporosis blocks the factors of Wnt signal-transduction pathway (sclerostin and Dkk1); it enhances the formation of osteoblasts and growth of bone tissue. ACE910 binds blood-coagulation factors IX and X and is designed to reduce bleeding rate in hemophilia A. The convergence of coagulation factors enhances the coagulation cascade. A Bispecific antibody against the transferrin receptor (provides passage through the blood-brain barrier) and protease BACE1 (accumulates amyloid peptides) is a candidate for an anti-Alzheimer's disease drug. Bispecific antibodies that are focused on autoimmune diseases usually bind cytokines: TNF, IL1, IL4, IL14, IL17, IL23, and others. It has been shown that simultaneous use of two mAbs against cytokines in autoimmune diseases has severe side effects without superior efficiency. In this regard, Bispecific antibodies against autoimmune diseases usually combine two anticytokine antigen-binding sites and provide higher therapeutic potential than a mixture of two mAbs. In particular, the most therapeutically important cytokines in psoriasis are IL17, IL23, IL6, and TNF. ABT122 against TNFα and IL17A has clinical effects in rheumatoid arthritis and psoriatic arthritis. In contrast, Phase I/II clinical trials of COVA322 (same specificity as ABT122) in psoriasis were preliminary terminated, due to safety concerns. Antigen-binding sites of ABT981 are directed against IL1α and IL1β, inflammatory cytokines found in the cartilage and synovial fluid of patients with osteoarthritis.

Bispecific antibodies have several significant advantages over monospecific Abs. Bispecific antibodies direct specific effectors of the immune system to target tumor cells, enhancing their cytotoxicity. Bispecific antibodies can provide higher binding specificity, since in contrast to monospecific Abs, they interact with two different surface antigens. The use of Bispecific antibodies compared to combination therapy with two monospecific drugs makes it possible to optimize expenses by reducing the cost of development and clinical trials. Since one disease modulator may play an essential role in several independent pathways and coexpression of different receptors has been found in many tumors, targeting of two different growth-promoting receptors on a single tumor cell may increase the antiproliferative effect and help to avoid the development of resistance.

Report Highlights

• In April 2023, Lonza signed an agreement with ABL Bio focusing on bispecific antibodies for immuno-oncology and neurodegenerative diseases. The collaboration is intended to help in the development and manufacturing of ABL Bio's new bispecific antibody product.
• In March 2023, InvoX Pharma Limited announced that F-star, an invoX company, entered into a second licence agreement with Takeda for a novel next-generation immuno-oncology bispecific antibody. Under the terms of the licence agreement, F-star will grant Takeda a worldwide, exclusive royalty-bearing licence to research, develop, and commercialize a bispecific antibody directed towards an undisclosed immuno-oncology target using F-star's proprietary Fcab™ and mAb2 platforms. Takeda will be responsible for all research, development and commercialisation activities under the agreement. F-star will receive an undisclosed upfront licence fee and is eligible to receive potential future development and commercialization milestone payments, plus royalties on annual net sales.
• In January 2023, Caris Life Sciences (Caris) and Xencor, Inc. announced an expansion of their collaboration to research, develop and commercialize novel XmAb® bispecific and multi-specific antibodies directed against novel targets, identified and proposed by Caris, for the treatment of patients with cancer.
• In December 2022, Akeso announced a collaboration and license agreement with Summit Therapeutics Inc., to out-license its breakthrough bispecific antibody, ivonescimab (PD-1/VEGF, AK112) for development and commercialization in the United States, Canada, Europe, and Japan (the "License Territories"). In addition, the Company will co-brand the product in the License Territories.
• In December 2022, Biogen announced that it had reached an agreement with Genentech, a member of the Roche Group, related to the commercialization and sharing of economics for glofitamab. Under the terms of the agreement, Biogen will have no payment obligations and will receive tiered royalties on potential net sales of glofitamab within the United States as part of the companies' long-standing collaboration on antibodies targeting CD20.
• In November 2022, IGM Biosciences and ADC Therapeutics announced that they had entered into a clinical trial collaboration and supply agreement to evaluate the combination of imvotamab, IGM's novel IgM CD20 x CD3 T cell engaging bispecific antibody, and ZYNLONTA® (loncastuximab tesirine-lpyl), ADC Therapeutics' CD19-directed antibody drug conjugate (ADC), for the treatment of patients with relapsed/refractory (R/R) B cell non-Hodgkin's lymphoma (NHL).
• In November 2022, Nona Biosciences announced that it had entered into a collaboration agreement with Dragonfly Therapeutics based on Nona's proprietary fully human heavy chain only antibody (HCAb) transgenic mice platform to discover and develop fully human heavy chain only antibodies for bispecific/multi-specific therapeutic antibody generation.
• In October 2022, Jazz Pharmaceuticals and Zymeworks Inc. had entered into an exclusive licensing agreement under which Jazz will acquire development and commercialization rights to Zymeworks' zanidatamab across all indications in the United States, Europe, Japan and all other territories except for those Asia/Pacific territories previously licensed by Zymeworks.
• In October 2022, Gilead Sciences and MacroGenics announced an exclusive option and collaboration agreement to develop MGD024, an investigational, bispecific antibody that binds CD123 and CD3 using MacroGenics' DART® platform, and two additional bispecific research programs. The collaboration agreement grants Gilead the option to license MGD024, a potential treatment for certain blood cancers, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

Bispecific antibody: Company and Product Profiles (Marketed Therapies)

1. Company Overview: Janssen

Janssen is creating a future where disease is a thing of the past. Janssen is the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. The company focus on areas of medicine where they can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.

Product Description: Amivantamab

Amivantamab is a fully human bispecific antibody that targets EGFR and Met, two validated cancer targets. In July 2012, Genmab entered into a collaboration with Janssen Biotech, Inc. to create and develop bispecific antibodies using Genmab's DuoBody® technology platform. The two antibody libraries used to produce amivantamab were both generated by Genmab. The antibody pair used to create Amivantamab was selected in collaboration between Genmab and Janssen. Subsequent development work was carried out by Janssen. In 2021, Janssen received approval from the U.S. FDA for amivantamab-vmjw (RYBREVANT®) for the treatment of adult patients with locally-advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) Exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. This is the first regulatory approval for a therapy that was created using Genmab's proprietary DuoBody bispecific technology platform.

2. Company Overview: Amgen

Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe, effective medicines from lab to manufacturing plant to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, bone disease and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and vital medicines.

Product Description: Blinatumomab

Blinatumomab (AMG 103) is a bispecific T cell engager (BiTE®) antibody designed to direct the body's cell-destroying T cells against target cells expressing CD19, a protein found on the surface of B-cell derived leukemias and lymphomas. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells to cancer cells. Blinatumomab is the first of the BiTE antibodies and Amgen has received orphan drug designation from the U.S. Food and Drug Administration for the treatment of ALL, chronic lymphocytic leukemia (CLL), hairy cell leukemia, prolymphocytic leukemia and indolent B cell lymphoma and from the European Medicines Agency for the treatment of indolent B cell lymphoma, ALL, CLL and mantle cell leukemia (MCL). The drug is approved for the treatment of Precursor B-cell lymphoblastic leukaemia-lymphoma. The drug is currently being evaluated for the treatment of Non-Hodgkin's lymphoma, diffuse large B cell lymphoma, and others.

Bispecific antibody: Company and Product Profiles (Pipeline Therapies)

1. Company Overview: Akeso

Akeso is a commercial-stage biopharmaceutical company committed to the discovery, development, manufacturing, and commercialization of innovative medicines with high unmet medical needs worldwide. Founded in 2012, the company has established a comprehensive in-house drug development platform (ACE Platform) and know-how, including R&D, clinical development, CMC (Chemistry, Manufacturing, and Controls), and commercialization capabilities. With fully integrated multi-functional platform, Akeso is internally working on a robust pipeline of over 30 innovative assets in the fields of cancer, autoimmune disease, inflammation, metabolic disease, and other major therapeutic areas.

Product Description: Ivonescimab

Ivonescimab, known as AK112 in China and Australia and also as SMT112 in the License Territories, is a novel, potential first-in-class bispecific antibody independently developed by the Company. Ivonescimab combines the power of immunotherapy via a blockade of PD-1 with the anti-angiogenesis benefits of an anti-VEGF into a single molecule. It is our belief that the novel design has the potential to reduce side effects and safety concerns. Ivonescimab is believed to be the PD-1 / VEGF bispecific antibody that is most advanced in the clinic: there are no known PD-1-based bispecific antibodies approved by the US Food and Drug Administration ("FDA") or the European Medicines Agency ("EMA"). Currently, Akeso is conducting a phase III clinical trial of ivonescimab monotherapy versus pembrolizumab monotherapy as the first-line treatment for NSCLC patients with positive PD-L1 expression. In addition, a phase III clinical trial of Ivonescimab plus chemotherapy versus chemotherapy in EGFR mutated advanced non-squamous NSCLC that failed in prior EGFR-TKI therapy is ongoing. Ivonescimab has received breakthrough therapy designation status in China from the NMPA for three indications: the two aforementioned indications, as well as combined with docetaxel for the treatment of locally advanced or metastatic NSCLC patients who failed to prior PD-(L)1 inhibitor combined with platinum-based doublet chemotherapy.

2. Company Overview: Zymeworks

Zymeworks is a clinical-stage biopharmaceutical company dedicated to the discovery, development and commercialization of next-generation multifunctional biotherapeutics. Zymeworks' suite of therapeutic platforms and its fully integrated drug development engine enable precise engineering of highly differentiated product candidates. Zymeworks is also advancing a deep preclinical pipeline in oncology (including immuno-oncology agents) and other therapeutic areas. In addition, its therapeutic platforms are being leveraged through strategic partnerships with global biopharmaceutical companies.

Product Description: Zanidatamab

Zanidatamab is a bispecific antibody, based on Zymeworks' Azymetric platform, which can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2 and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2.

3. Company Overview: Roche

Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world's largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. The company is a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects the efforts to improve access to healthcare together with local partners in every country. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.

Product Description: Glofitamab

Glofitamab is an investigational CD20xCD3 T-cell engaging bispecific antibody being developed by Roche for the treatment of B-cell non-Hodgkin's lymphomas, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and other blood cancers1. Glofitamab is based on a novel structural format called ‘2:1', which is engineered to have two ‘Fab' regions that bind to CD20 and one ‘Fab' region which binds to CD3. This dual targeting activates and redirects a patient's own T-cells to engage and eliminate cancer B cells. Data from the Phase II NP30179 study investigating glofitamab in patients with relapsed/refractory (R/R) DLBCL have been submitted for review to the European Medicines Agency (EMA), and submissions to additional health authorities worldwide, including the U.S. Food and Drug Administration, are ongoing. If approved, glofitamab has the potential to be a first-in-class fixed-duration CD20xCD3 T-cell engaging bispecific antibody in DLBCL. Genentech will have sole decision-making rights on the commercialization of glofitamab within the United States and, in the event of approval, Biogen is eligible to receive tiered royalties in the mid-single digits range on potential net sales of glofitamab within the United States.

Glofitamab, together with mosunetuzumab, is part of the Roche and Genentech CD20xCD3 antibody portfolio that seeks to address the unmet needs of people living with blood cancers. In January 2022, Biogen exercised the option to have joint decision-making rights related to the development and potential commercialization of mosunetuzumab, and Genentech will continue to lead the strategy and implementation of the program. The companies have had a collaboration on antibodies targeting CD20 since 1995.

4. Company Overview: IGM Biosciences

IGM Biosciences is a clinical-stage biotechnology company committed to developing and delivering a new class of medicines to treat patients with cancer, infectious diseases and autoimmune and inflammatory diseases. The Company's pipeline of clinical and preclinical assets is based on the IgM antibody, which has 10 binding sites compared to conventional IgG antibodies with only 2 binding sites. The Company also has an exclusive worldwide collaboration agreement with Sanofi to create, develop, manufacture, and commercialize IgM antibody agonists against oncology and immunology and inflammation targets.

Product Description: Imvotamab

Imvotamab is a novel IgM-based CD20 x CD3 bispecific antibody T cell engager (TCE) with the therapeutic potential to be a backbone treatment in hematology. Preclinical research demonstrates that imvotamab may have advantages over IgG bispecific antibodies including greater binding power to CD20 expressing cancer cells especially when CD20 expression has been reduced due to prior treatment with anti-CD20 antibodies. It has also been shown to have good target cell killing efficacy combined with a lower cytokine release profile associated with the T cell directed cellular cytotoxicity (TDCC) mechanism. Data generated from Phase 1 clinical trials provide evidence that imvotamab exhibits a favorable safety and tolerability profile with promising activity in refractory or relapsed NHL patients. Imvotamab is currently being studied in two Phase II trials to assess the safety and efficacy of two doses 100 mg and 300 mg, in patients with diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL).

5. Company Overview: MacroGenics

MacroGenics is a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer. The company generates its pipeline of product candidates primarily from its proprietary suite of next-generation antibody-based technology platforms, which have applicability across broad therapeutic domains. The combination of MacroGenics' technology platforms and protein engineering expertise has allowed the company to generate promising product candidates and enter into several strategic collaborations with global pharmaceutical and biotechnology companies.

Product Description: MGD024

MGD024 is an investigational, next-generation, bispecific CD123 × CD3 DART® molecule that engages CD3 on immune effector cells to kill CD123-expressing cancer cells in certain hematological malignancies, including acute myeloid leukemia (AML). MGD024 was designed to minimize cytokine-release syndrome, while maintaining anti-tumor cytolytic activity, and permitting intermittent dosing through a longer half-life. In December 2021, the company presented preclinical MGD024 data at the American Society of Hematology (ASH) Annual Meeting that showed the potential for anti-tumor activity from the combination of MGD024 with standard of care agents used to treat AML. MacroGenics initiated a Phase I study of MG024 in patients with hematologic malignancies in 2022. In October 2022, MacroGenics announced that it had entered into an exclusive option and collaboration agreement with Gilead to develop MGD024 and two additional bispecific research programs. MacroGenics is responsible for the ongoing Phase I study for MGD024 during which Gilead may elect to exercise its option to license the program at predefined decision points.

Bispecific antibody Analytical Perspective

In-depth Commercial Assessment: Bispecific antibody Collaboration Analysis by Companies

The Report provides in-depth commercial assessment of drugs that have been included, which comprises collaboration, agreement, licensing and acquisition - deals values trends. The sub-segmentation is described in the report which provide company-company collaboration (licensing/partnering), company academic collaboration and acquisition analysis in tabulated form.

Bispecific antibody Competitive Landscape

The report comprises of comparative assessment of Companies (by therapy, development stage, and technology).

Bispecific antibody Report Assessment

• Company Analysis
• Therapeutic Assessment
• Pipeline Assessment
• Inactive drugs assessment
• Unmet Needs

Key Questions Answered

Current Treatment Scenario and Emerging Therapies:

• How many companies are developing Bispecific antibody drugs?
• How many Bispecific antibody drugs are developed by each company?
• How many emerging drugs are in mid-stage, and late-stage of development for the treatment of Bispecific antibody?
• What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the Bispecific antibody therapeutics?
• What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies?
• What are the clinical studies going on for Bispecific antibody and their status?
• What are the key designations that have been granted to the emerging and approved drugs?

Key Players

• Janssen
• Amgen
• Akeso
• Zymeworks
• Roche
• IGM Biosciences
• MacroGenics
• Provention Bio
• Jiangsu Alphamab Biopharmaceuticals
• Sichuan Baili Pharmaceutical
• Regeneron Pharmaceuticals
• Boehringer Ingelheim

Key Products

• Amivantamab
• Blinatumomab
• Ivonescimab
• Zanidatamab
• Glofitamab
• Imvotamab
• MGD024
• PRV 3279
• KN-046
• SI-B001
• REGN-5458
• BI-905711

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