Monoclonal antibodies - Competitive landscape, 2023

This “Monoclonal antibodies - Competitive landscape, 2023” report provides comprehensive insights about 180+ companies and 230+ drugs in Monoclonal antibodies 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

Monoclonal antibodies: Understanding

Monoclonal antibodies: Overview

The immune system has multifunctional units referred to as antibodies, mostly polyclonal which facilitate humoral and cellular reactions to antigens. However, it is possible to produce large quantities of an antibody from a single B-cell clone which are called as Monoclonal Antibodies (MAbs). Using these antibodies for therapeutic purposes is termed as Immunotherapy. The usage of the monoclonal antibodies in cancer therapy requires the understanding of the biological role of various antigens involved in tumor growth. Monoclonal antibody (mAb) allows far more precise understanding of the humoral immune response by allowing dissection of this response into its individual B-lymphocyte populations. A large number of mAbs have been produced against renal, bladder, and prostate cancer antigens. There are several ways by which the mAbs are made. They are as follows: i) Human: Theses are derived from the human source. Called as ‘umabs'. ii) Murine: These are derived from mouse. Called as ‘omabs'. Iii) Humanized: Here the mouse proteins are attached to the human protein. Called as ‘zumabs' iv) Chimeric: variable regions are from humans and constant regions are from mouse. Called as ‘ximabs.'

An antibody molecule has a Y-shaped structure with a total molecular weight of ~150 kDa, composed of four polypeptide chains including two identical heavy (H) and two light (L) chains. Covalent bonds (mainly disulfide interactions) provide the stability of heavy and light chains next to each other. Each heavy or light chain is composed of constant (CH and CL, respectively) and variable domains (VH and VL, respectively). Each antibody has two identical arms known as “antigen binding fragments” or Fabs, acting as antigen-binding sites. Each Fab consists of a variable region known as Fv (formed by the VH and VL domains), and the constant region (formed by the CH and CL domains). Therefore, several functions are explained by which antibodies can eliminate a particular antigen and both variable and constant regions of antibodies contribute to this response. The stability and flexibility of antibodies and their effector functions such as activating ADCC, CDC, as well as interaction with C1q are important factors determining the suitability of immunoglobulins for the development of therapeutic mAbs. The majority of the clinically available mAbs are IgG.

Attention to therapeutic monoclonal antibodies has been dramatically increasing year by year. Their highly specific targeting of antigens can provide very effective medical treatment, and the advent of molecular-targeting medicine is allowing development of a new generation of therapeutic agents. However, there is one critical obstacle to overcome. Most of the established therapeutic monoclonal antibodies have specificity for the primary structures of target antigens, although all proteins harbor original native intact structures for their own specific functions. Stereo-specific monoclonal antibodies recognizing conformational structures of target antigens may thus offer a markedly more versatile approach. Their application may change the very concepts underlying use of therapeutic antibodies.

Report Highlights

• In March 2023, Shanghai - Jacos Pharmaceuticals (1167.HK) announced a clinical collaboration with Merck to evaluate the combination therapy of Si's CD73 monoclonal antibody JAB-BX102 and Merck's PD-1 inhibitor KEYTRUDA (pembrolizumab). This clinical study will evaluate the clinical effect of JAB-BX102 in combination with KEYTRUDA in advanced solid tumors. Under the terms of the agreement, Merck will provide KEYTRUDA.
• In March 2023, Simcere Pharmaceutical Group Limited (2096.HK) announced that Simcere Zaiming, an innovative oncology pharmaceutical company of Simcere has entered into a clinical collaboration agreement with MSD (Merck & Co., Inc., Rahway, NJ, USA) to evaluate the combination of SIM0235, a potential first-in-class humanized anti-tumor necrosis factor receptor 2 (TNFR2) monoclonal antibody, and MSD's anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with advanced solid tumors and cutaneous T-cell lymphoma (CTCL).
• In March 2023, BioNTech SE and OncoC4 announced that they had entered into an exclusive worldwide license and collaboration agreement to develop and commercialize OncoC4's next-generation anti-CTLA-4 monoclonal antibody candidate, ONC-392, as monotherapy or combination therapy in various cancer indications. The transaction is expected to close in the first half of 2023, subject to customary closing conditions and regulatory clearances.
• In February 2023, Vir Biotechnology announced that the research collaboration agreement established with GSK in 2020 had been amended to reflect that Vir will continue its ongoing efforts to discover, develop and advance next-generation solutions for COVID-19 and other potential coronavirus outbreaks, independently or with other partners. Together, the Companies will continue working to ensure ongoing access to sotrovimab for patients around the world, where authorized, and to develop new therapies for influenza and other respiratory diseases.
• In January 2023, CARsgen Therapeutics Holdings Limited announced CARsgen's execution of a collaboration agreement with F. Hoffmann-La Roche Ltd ("Roche") to evaluate CARsgen's investigational drug AB011, that received IND clearance globally, in combination with atezolizumab, Roche's PD-L1 checkpoint inhibitor, along with standard-of-care chemotherapy in patients with gastric or gastroesophageal junction carcinoma. Under the terms of the agreement, Roche will be responsible for operation and conduct of the trial while both companies co-share the costs of the AB011 treatment arms in the study. As part of the clinical collaboration, CARsgen's proprietary CLDN18.2 IHC test kit, which has showed excellent specificity and sensitivity profiles, will be applied to evaluate CLDN18.2 expression in the gastric cancer patients.
• In November 2022, Exelixis and Sairopa announced that the companies had entered into an exclusive clinical development and option agreement for ADU-1805, a potentially best-in-class monoclonal antibody that targets SIRPα. SIRPα expressed on myeloid cells interacts with CD47 present on the surface of cancer cells and blocks the ability of macrophages to clear tumor cells via phagocytosis and inhibits tumor antigen presentation to T-cells. Blocking SIRPα has the potential to improve the immune system's ability to attack tumors by addressing a significant immune-suppressive component of the tumor microenvironment.
• In October 2022, Compass Therapeutics, announced a clinical trial collaboration and supply agreement with Merck (known as MSD outside the United States and Canada). The collaboration enables the evaluation of the safety and efficacy of Compass' CTX-471, a fully human monoclonal antibody that binds and activates a novel epitope of the co-stimulatory receptor CD137 (expressed on T cells and NK cells) in combination with Merck's anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in a Phase 1b trial. Under the agreement, Compass is the study sponsor, and Merck will provide the clinical supply of KEYTRUDA; the companies will form a Joint Development Committee to review the clinical trial results.
• In September 2022, Abpro announced a strategic partnership with Celltrion for its cancer molecule ABP 102, an antibody therapy for patients suffering from HER2+ cancer, including breast, gastric, and pancreatic cancer. Through this global partnership, Abpro will receive payments from Celltrion of up to $1.75 Billion, including an equity investment, development and commercial milestone payments and worldwide profit sharing. Celltrion will be in charge of the development of ABP 102 following the completion of in vitro studies by Abpro and will have world-wide commercialization rights. HER2+ type cancer is implicated in up to 30% of all cases in breast, gastric, pancreatic, and other forms of cancer.

Monoclonal antibodies: Company and Product Profiles (Marketed Therapies)

1. Company Overview: Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies' strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies - as single agents and combination regimens - for patients with cancer in Japan, South Korea and Taiwan. Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

Product Description: OPDIVO

OPDIVO is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body's own immune system to help restore anti-tumor immune response. By harnessing the body's own immune system to fight cancer, OPDIVO has become an important treatment option across multiple cancers. OPDIVO's leading global development program is based on Bristol-Myers Squibb's scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. In July 2014, OPDIVO was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. OPDIVO is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company's OPDIVO and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma. In March 2022, Bristol Myers Squibb announced that the US Food and Drug Administration (FDA) approved OPDIVO (nivolumab) 360 mg (injection for intravenous use) in combination with platinum-doublet chemotherapy every three weeks for three cycles for adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) in the neoadjuvant setting.

2. Company Overview: GSK

GSK is a fully focused biopharma company. The company prioritize innovation in vaccines and specialty medicines, maximizing the increasing opportunities to prevent and treat disease. The R&D focus on the science of the immune system, human genetics and advanced technologies, and our world-leading capabilities in vaccines and medicines development. The company focuses on four therapeutic areas: infectious diseases, HIV, immunology/respiratory, and oncology.

Product Description: NUCALA

NUCALA (Mepolizumab) is an IL-5 antagonist (IgG1 kappa). IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Mepolizumab binds to IL-5 with a dissociation constant of 100 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface. Inflammation is an important component in the pathogenesis of asthma, CRSwNP, EGPA, and HES. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) are involved in inflammation. By inhibiting IL-5 signaling, Mepolizumab reduces the production and survival of eosinophils. Mepolizumab has been developed for the treatment of diseases that are driven by inflammation caused by eosinophils. It has been studied in over 4,000 patients in 41 clinical trials across a number of eosinophilic indications and has been approved under the brand name Nucala in the US, Europe and in over 20 other markets, as an add-on maintenance treatment for patients with SEA. It is approved for paediatric use in SEA from ages six to 17 in Europe, the US and several other markets. In the US, Japan, Canada and a number of other markets, it is approved for use in adult patients with EGPA. Mepolizumab was approved for use in HES in the US in September 2020, followed by Brazil in February 2021 and Argentina in May 2021. Currently, Mepolizumab is being evaluated in the Phase III to treat patients with chronic obstructive pulmonary disease and is in Phase II for the treatment of Eosinophilic oesophagitis.

Monoclonal antibodies: Company and Product Profiles (Pipeline Therapies)

1. Company Overview: Novartis

Novartis is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world.

Product Description: Ianalumab

Ianalumab (VAY736) is a novel, defucosylated, human IgG1/κ monoclonal antibody that targets the human B cell-activating factor (BAFF) of the TNF family. The BAFF receptor is predominantly expressed on B cells and is critically involved in B cell maturation, activation, and survival. VAY736 targets the BAFF receptor and competitively inhibits BAFF binding to BAFF-R, thereby blocking BAFF-R-mediated signaling in B cells. It is also engineered to effectively eliminate B cells from circulation in vivo by antibody-dependent cellular cytotoxicity (ADCC). ADCC activity of ianalumab is greatly enhanced by eliminating fucose residues from the carbohydrate moiety attached to the Fc part of the antibody. It is currently in Phase III clinical studies for the treatment of Sjögren's Syndrome (SS), Lupus nephritis, Immune thrombocytopenia, Systemic lupus erythematosus, and warm autoimmune hemolytic anemia. Along with this, the molecule is also being studied in the Phase II development for the Idiopathic pulmonary fibrosis, Multiple sclerosis, and others.

2. Company Overview: Novo Nordisk

Novo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. The purpose is to drive change to defeat diabetes and other serious chronic diseases such as obesity and rare blood and endocrine disorders. They do so by pioneering scientific breakthroughs, expanding access to the medicines and working to prevent and ultimately cure disease. Novo Nordisk employs about 50,800 people in 80 countries and markets its products in around 170 countries.

Product Description: Ziltivekimab

Ziltivekimab is a proprietary anti-interleukin-6 ligand monoclonal antibody (anti-IL6 mAb), targeting residual inflammatory cardiovascular risk in patients living with advanced chronic kidney disease (CKD). Ziltivekimab is being developed a therapy intended to reduce the risk of major cardiovascular adverse events in chronic kidney disease (CKD) patients with atherosclerotic cardiovascular disease (ASCVD) and inflammation. Patients who are diagnosed with moderate to severe CKD and have ASCVD and inflammation are at risk for an adverse cardiovascular event at a high rate and there are no approved therapies to prevent this risk. The proinflammatory cytokine, interleukin-6 (IL-6) has been shown to be an independent, causal factor of ASCVD with evidence generated from human genetic studies and preclinical studies. The drug is being evaluated in Phase III stage of development to treat patients with moderate to severe chronic kidney disease.

3. Company Overview: Novartis

Novartis is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world.

Product Description: Iscalimab

Iscalimab (CFZ 533) is a novel, fully human IGg1 anti-CD40 monoclonal antibody, preventing cluster of differentiation (CD40) pathway signaling and activation of CD40+ cell types. This molecule is expressed on antigen-presenting cells, such as macrophages, dendritic cells, and B cells, while its ligand CD40L is expressed on activated T cells. CD40L induces activation of B cells, immunoglobulin class switch, plasma cell differentiation, as well as GC formation. It is being developed by Novartis and investigating this therapeutic molecule in the phase II stage of development to treat patients with Sjorgen's Syndrome, Type 1 Diabetes mellitus, and Hidradenitis suppurativa, Graves' disease, Liver transplant rejection, and others.

4. Company Overview: Disc Medicine

Disc Medicine is a clinical-stage biopharmaceutical company committed to discovering, developing, and commercializing novel treatments for patients who suffer from serious hematologic diseases. We are building a portfolio of innovative, first-in-class therapeutic candidates that aim to address a wide spectrum of hematologic diseases by targeting fundamental biological pathways of red blood cell biology, specifically heme biosynthesis and iron homeostasis.

Product Description: DISC-0974

DISC-0974 is an investigational monoclonal antibody (mAb) targeting a BMP-signaling co-receptor called hemojuvelin (HJV) and is designed to suppress hepcidin production and increase serum iron levels in patients suffering from anemia of inflammation. DISC-0974 was in-licensed by Disc from AbbVie in 2019. Anemia of inflammation arises from abnormally elevated hepcidin and is the most common form of anemia, affecting millions of patients in the US across numerous diseases such as chronic kidney disease, myelofibrosis, cancer, autoimmune diseases, and other conditions with an inflammatory component. Disc has established clinical proof-of-mechanism of DISC-0974 in a Phase I trial of healthy volunteers and initiated a Phase Ib/IIa clinical trial of DISC-0974 in patients with myelofibrosis and anemia, as well as a Phase Ib/IIa clinical trial of DISC-0974 in patients with chronic kidney disease and anemia who are not receiving dialysis.

5. Company Overview: Chinook Therapeutics

Chinook Therapeutics, Inc. is a clinical-stage biotechnology company developing precision medicines for kidney diseases. The company's pipeline is focused on rare, severe chronic kidney disorders with opportunities for well-defined and streamlined clinical pathways. Chinook's lead program is atrasentan, an investigational endothelin receptor antagonist in development for the treatment of IgA nephropathy and other primary glomerular diseases. The company is also advancing a preclinical development candidate for an undisclosed ultra-orphan kidney disease and research programs for other rare, severe chronic kidney diseases, including polycystic kidney disease. Chinook seeks to build its pipeline by leveraging insights in kidney single cell RNA sequencing, human-derived organoids and new translational models, to discover and develop therapeutics with mechanisms of action against key kidney disease pathways. Chinook is backed by leading healthcare investors, Versant Ventures, Apple Tree Partners, and Samsara BioCapital, and is based in Vancouver, British Columbia and Seattle, Washington.

Product Description: BION-1301

BION-1301, an investigational humanized IgG4 monoclonal antibody that blocks APRIL binding to both the BCMA and TACI receptors, is being evaluated in IgA nephropathy. Dosing of BION-1301 in non-human primates led to a significant reduction of blood IgA levels and established a favorable safety profile. Preclinical studies demonstrated that hAPRIL transgenic mice produce rising levels of IgA as well as IgA deposits in the kidney. Administration of mouse anti-human APRIL was shown to reduce levels of IgA in both the serum and the kidney.

The safety and tolerability of BION-1301 were evaluated in a phase 1 trial in healthy volunteers. In healthy volunteers, BION-1301 was well-tolerated with no serious adverse events, a pharmacokinetic half-life of approximately 33 days and demonstrated dose-dependent pharmacodynamic effects characterized by durable reductions in serum levels of free APRIL, IgA, galactose-deficient IgA (Gd-IgA1) and IgM, with a lesser reduction in IgG. BION-1301 is currently being evaluated in a phase I/II clinical trial in patients with IgA nephropathy. Preliminary data from the first cohort of patients with IgA nephropathy demonstrated that BION-1301 has been well-tolerated to date, with no serious adverse events or treatment discontinuations due to adverse events. The pharmacokinetics of BION-1301 observed in patients with IgAN were consistent with those previously reported in healthy volunteers and sufficient to drive rapid and sustained reductions in free APRIL levels. BION-1301 durably reduced Gd-IgA1, IgA, IgM, and to a lesser extent, IgG levels in patients with IgAN. BION-1301 treatment resulted in proteinuria reductions within three months, which were sustained and continued to decline through one year in patients across a range of disease severity.

Monoclonal antibodies Analytical Perspective

In-depth Commercial Assessment: Monoclonal antibodies 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.

Monoclonal antibodies Competitive Landscape

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

Monoclonal antibodies 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 Monoclonal antibodies drugs?
• How many Monoclonal antibodies drugs are developed by each company?
• How many emerging drugs are in mid-stage, and late-stage of development for the treatment of Monoclonal antibodies?
• What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the Monoclonal antibodies 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 Monoclonal antibodies and their status?
• What are the key designations that have been granted to the emerging and approved drugs?

Key Players

• Novartis
• Gmax Biopharm
• Omeros Corporation
• Merck Sharp & Dohme
• Disc Medicine
• Eledon Pharmaceuticals
• Alexion AstraZeneca Rare Disease
• Chinook Therapeutics
• Omeros Corporation
• Novo Nordisk
• Merck KGaA
• Bristol-Myers Squibb
• Jacobio Pharmaceuticals

Key Products

• Ianalumab
• GMA-131
• anti-MASP-2 monoclonal antibody
• MK-2060
• DISC-0974
• AT-1501
• Ravulizumab
• BION 1301
• Narsoplimab
• Pembrolizumab
• Ziltivekimab
• Opdivo
• Avelumab
• JAB-BX102