Antibody Drug Conjugate - Competitive landscape, 2023

This “Antibody Drug Conjugate- Competitive landscape, 2023,” report provides comprehensive insights about 180+ companies and 290+ drugs in Antibody Drug Conjugate 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

Antibody Drug Conjugate: Understanding

Antibody Drug Conjugate: Overview

Antibody-drug conjugates (ADC) are one of the fastest growing anticancer drugs. This approach comprises a mAb conjugated to the cytotoxic payload via a chemical linker that directed toward a target antigen expressed on the cancer cell surface, reducing systemic exposure and therefore toxicity. ADCs are complex molecules that require careful attention to various components. Selection of an appropriate target, an mAb, cytotoxic payload, and the manner in which the antibody is linked to the payload are key determinants of the safety and efficacy of ADCs. Antibody-drug conjugate (ADC) is a new emerging class of highly potent pharmaceutical drugs, which is a great combination of chemotherapy and immunotherapy. The concept of ADC was first presented by the German physician and scientist Paul Ehrlich almost 100 years before. One of the most important aspects of ADC development for cancer is the identification of the unique antigenic target of the mAb component. There are 328 unique antigens used in antibody-based therapy as a target. The selected antigen needs to fulfill several requirements. First, the target antigen needs to have high expression in the tumor and no or low expression in the healthy cell. Second, the target antigen should be displayed on the surface of the tumor cell to be available to the circulated mAb. Third, the target antigen should possess internalization properties as it will facilitate the ADC to transport into the cell, which will in turn enhance the efficacy of the cytotoxic agent. In ADCs, the most targeted antigens are ERBB2, CD19, CD33, CD22, and MSLN (mesothelin). In addition, over 50 different known antigens have been used in ADC as a target. However, previous studies showed that some tumor antigens also show low expression in the normal cell. The idea behind ADCs is the optimal delivery of a highly potent payload to its target using a specific carrier. Administration of ADCs is done intravenously into the bloodstream to avoid gastric acid and proteolytic enzyme degradation of the mAb. Ideally, exclusive expression of the target antigens on tumor cells, but not on normal cells, is the prerequisite for the mAb component of ADCs to find and bind to it. Upon recognition and attaching to its target, internalization of the ADC-antigen complex into the cell takes place via receptor-mediated endocytosis. Internalization takes place via three different routes: (i) clathrin-mediated endocytosis (the major route of intracellular uptake of ADCs), (ii) caveolae-mediated endocytosis, and (iii) pinocytosis. The rate and efficiency of the ADC-antigen complex to be internalized depends on the type of target and the cytotoxic compounds. Insufficient affinity (Kd > 10 nmol/L), in case of low binding affinity that does not result in binding to the receptor, may result in inefficient internalization leading to the off-target release of ADC and therefore results in systemic toxicity.

Report Highlights

• In April 2023, Mythic Therapeutics, announced preclinical data highlighting the potential of MYTX-011, its investigational cMET-targeting ADC, for treating a broader range of cMET+ cancers than other cMET-targeting ADCs in development. These data were presented as a poster at the American Association for Cancer Research Annual Meeting. MYTX-011 demonstrated higher internalization in cMET+ tumor cells and broader, more potent efficacy, including a greater than 3-fold increase in efficacy in mouse models of NSCLC, as compared to other cMET-targeting ADCs.
• In April 2023, Araris Biotech AG, announced the company delivered two poster presentations at this year's American Association for Cancer Research (AACR) 2023 Annual Meeting, being held April 14-19, 2023 at the Orange County Convention Center in Orlando, Florida. The presentations highlighted late-breaking preclinical data on anti-Nectin-4 and anti-HER2 ADCs generated using the company's proprietary linker technology. Both ADCs demonstrated improved anti-tumor activity compared to respective FDA approved ADCs in head-to-head in-vivo studies.
• In March 2022, Sanofi and Seagen Inc. announced an exclusive collaboration agreement to design, develop, and commercialize antibody-drug conjugates (ADCs) for up to three cancer targets. The collaboration will utilize Sanofi's proprietary monoclonal antibody (mAb) technology and Seagen's proprietary ADC technology. ADCs are antibodies engineered to deliver potent anti-cancer drugs to tumor cells expressing a specific protein and Sanofi currently has one ADC in development.
• In December 2022, Merck and Kelun-Biotech, announced that the companies have entered into an exclusive license and collaboration agreement to develop seven investigational preclinical antibody-drug conjugates (ADC) for the treatment of cancer. Under the agreement, Kelun-Biotech has granted Merck exclusive global licenses to research, develop, manufacture and commercialize multiple investigational preclinical ADC therapies and exclusive options to obtain additional licenses to ADC candidates. Kelun-Biotech retains the right to research, develop, manufacture and commercialize certain licensed and option ADCs for mainland China, Hong Kong and Macau.
• In December 2022, Biosion USA, Inc. announced an exploratory research collaboration to create antibody-drug conjugates (ADCs) for the treatment of cancer with ImmunoGen, Inc., a leader in developing next generation ADCs. In the joint research effort, Biosion leveraged its proprietary SynTracer® high-throughput (HT) endocytosis platform to generate highly selective antibodies to targets allocated by each company and ImmunoGen will provide their proprietary linker-payload technology to create novel ADCs.

Antibody Drug Conjugate: Company and Product Profiles (Marketed Therapies)

1. Company Overview: Pfizer

Pfizer Oncology is committed to pursuing innovative treatments that have a meaningful impact on those living with cancer. As a leader in oncology speeding cures and accessible breakthrough medicines to patients, Pfizer Oncology is helping to redefine life with cancer. The strong pipeline of biologics, small molecules and immunotherapies, one of the most robust in the industry, is studied with precise focus on identifying and translating the best scientific breakthroughs into clinical application for patients across a wide range of cancers. By working collaboratively with academic institutions, individual researchers, cooperative research groups, governments and licensing partners, Pfizer Oncology strives to cure or control cancer with its breakthrough medicines. Because Pfizer Oncology knows that success in oncology is not measured solely by the medicines you manufacture, but rather by the meaningful partnerships you make to have a more positive impact on people's live.

Product Description: MYLOTARG

MYLOTARG is an antibody-drug conjugate (ADC) composed of the cytotoxic agent calicheamicin, attached to a monoclonal antibody (mAB) targeting CD33, an antigen expressed on the surface of myeloblasts in up to 90 percent of AML patients. When MYLOTARG binds to the CD33 antigen on the cell surface it is absorbed into the cell and calicheamicin is released causing cell death. MYLOTARG was approved by the U.S. Food and Drug Administration in September 2017 for adults with newly diagnosed CD33-positive acute myeloid leukemia (AML), and adults and children 2 years and older with relapsed or refractory CD33-positive AML. MYLOTARG originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development and commercialization activities for this molecule. Pfizer also collaborated with SFJ Pharmaceuticals Group on the registrational program for MYLOTARG.

2. Company Overview: AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. Daiichi Sankyo Company, Limited and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan. Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings.

Product Description: Enhertu

Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo's proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca's ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker. Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridisation [ISH]-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. Enhertu (5.4mg/kg) is approved under accelerated approval in the US for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer whose tumours have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu (6.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial and/or DESTINY-Gastric02 trial.

Antibody Drug Conjugate: Company and Product Profiles (Pipeline Therapies)

1. Company Overview: Jiangsu Hengrui Medicine Co Ltd.

Jiangsu Hengrui Medicine Co Ltd (Jiangsu Hengrui) is a biopharmaceutical company that focuses on the research, development, manufacture, and distribution of novel pharmaceutical products. Its product portfolio includes anti-tumor drugs, surgical drugs, contrast agents, angiomyocardiac drugs, and antibiotics. The company is also developing pipeline products for the treatment of cancer, Crohn's disease, anemia, diabetes, atopic dermatitis, chronic bone disease, blood pressure, and hypercholesterolemia. Jiangsu Hengrui has R&D facilities in China, the US, and Japan. The company offers products through its sales and distribution network in China, the US, Japan, Germany Switzerland, and Australia. Jiangsu Hengrui is headquartered in Lianyungang, Jiangsu Province, China.

Product Description: SHR-A1811

SHR-A1811 is an innovative HER2-targeted antibody-drug conjugate with a topoisomerase I payload conjugated to an anti-HER-2 mAb by a cleavable linker. Once bound to HER2 expressing tumor cells, the ADC is internalized and the linker releases the toxin, leading to tumor cell death. It can bind to the cell membrane surface of HER2 expressing cells, and then enter the cells to reach the lysosome to release small Molecular toxins eventually induce tumor cell apoptosis, combining the high targeting of antibodies and the powerful killing power of cytotoxic drugs on target cells.

Preclinical research results show that SHR-A1811 has good anti-tumor activity, safety, tolerability and pharmacokinetic characteristics, or can further improve drug resistance, enhance efficacy, meet clinical needs, and provide more cancer patients multiple choice. Currently, the drug is in the Phase III stage of its development for the treatment of HER2 positive breast cancer. The drug is also being evaluated for the treatment of gynaecological cancer, gastric cancer, non-small cell lung cancer, oesophageal cancer, and solid tumors.

2. Company Overview: Seagen Inc.

Seagen, formerly Seattle Genetics, is a biotechnology company that discovers, develops, and markets monoclonal antibody-based therapies for the treatment of cancer. It markets antibody-drug conjugates (ADCs), including Adcetris (brentuximab vedotin), for the treatment of Hodgkin's lymphoma, T-cell lymphomas and CD30-expressing lymphomas; Padcevtm (enfortumab vedotin-ejfv) for metastatic urothelial cancers; Tukysa (tucatinib) for the treatment of metastatic HER2-positive breast cancers, and Tivdak (tisotumab vedotin-tftv) for the treatment of certain metastatic cervical cancers. The company's pipeline consists of novel therapies for addressing the unmet medical needs of blood-related cancers and solid tumors. Seagen products and pipeline are based on ADC technology, which targets monoclonal antibodies and delivers agents for killing cancer cells. The company sells its products through specialty distributors. Seagen is headquartered in Bothell, Washington, the US.

Product Description: Ladiratuzumab Vedotin

Ladiratuzumab vedotin is a novel investigational ADC targeted to LIV-1. Most metastatic breast cancers express LIV-1, which also has been detected in several other cancers, including lung, head and neck, esophageal and gastric. Ladiratuzumab vedotin utilizes Seattle Genetics' proprietary ADC technology and consists of a LIV-1-targeted monoclonal antibody linked to a potent microtubule-disrupting agent, monomethyl auristatin E (MMAE) by a protease-cleavable linker. This novel ADC is designed to bind to LIV-1 on cancer cells and release the cell-killing agent into target cells upon internalization. Ladiratuzumab vedotin may also cause antitumor activity through other mechanisms, including activation of an immune response by induction of immunogenic cell death. Currently the drug is in Phase II stage of Clinical trial evaluation for the treatment of Unresectable Locally Advanced or Metastatic Solid Tumors.

3. Company Overview: ImmunoGen, Inc.

ImmunoGen is developing the next generation of antibody-drug conjugates (ADCs) to improve outcomes for cancer patients. By generating targeted therapies with enhanced anti-tumor activity and favorable tolerability profiles, ImmunoGen, Inc. aim to disrupt the progression of cancer and offer the patients more good days. ImmunoGen, Inc. believe ADCs have a promising and durable role in cancer care. This belief has driven the work for over four decades. It's what has led to the leadership position in the ADC field, and it's why everything ImmunoGen, Inc. do is about developing the most precise, targeted cancer therapies.

Product Description: IMGN151

IMGN151 is a next-generation Antibody-drug Conjugate designed to address the unmet needs of cancer patients with tumor types expressing lower levels of folate receptor alpha (FRα). The investigational drug comprises an asymmetric, bivalent, biparatopic antibody targeting two independent epitopes of FRα, linked to a highly potent maytansinoid derivative, DM21, via a cleavable peptide linker with enhanced stability, longer half-life, and increased bystander activity. IMGN151 activity was characterized against cell lines and xenograft models with a wide range of FRα expression and compared to IMGN853. In in vitro studies, both IMGN151 and mirvetuximab soravtansine had similar activity against FRα-high KB cells. However, IMGN151 was up to 200 times more active against four FRα-medium cell lines. Furthermore, IMGN151 had also notably stronger bystander killing activity in a mixed culture of target-positive and negative cells. In in vivo studies, IMGN151 induced complete tumor regressions of human tumor xenograft models with high (KB, H-score of 300), medium (Igrov-1 and Ishikawa, H-score of 140 and 100, respectively) and low (Ov-90, H-score of 30) FRα expression. All tested doses were well tolerated with no body weight loss observed. Currently the drug is in Phase I stage of Clinical trial evaluation for the treatment of Endometrial Cancer.

4. Company Overview: Daiichi Sankyo

Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging the world class science and technology for the purpose “to contribute to the enrichment of quality of life around the world.” In addition to the current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.”

Product Description: DS-6000

DS-6000 is an investigational potential first-in-class CDH6 directed ADC and one of five ADCs in clinical development in the oncology pipeline of Daiichi Sankyo. Designed using Daiichi Sankyo's proprietary DXd ADC technology, DS-6000 is comprised of a humanized anti-CDH6 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Daiichi Sankyo is developing DS-6000 through a strategic collaboration with Sarah Cannon Research Institute with study operational oversight and delivery provided through Sarah Cannon's early phase oncology clinical research organization, Sarah Cannon Development Innovationsin Nashville, TN. CDH6 (human cadherin-6) is a cadherin family protein overexpressed in several cancers, particularly ovarian tumors and renal cell carcinoma. Overexpression of CDH6 is associated with tumor growth and proliferation and is correlated with poor prognosis in patients with renal cell carcinoma. No CDH6 directed cancer therapies are currently approved for treatment of any cancer. Currently, the drug is in the Phase I stage of its development for the treatment of Solid tumors.

Antibody Drug Conjugate: Analytical Perspective

In-depth Commercial Assessment: Antibody Drug Conjugate: 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.

Antibody Drug Conjugate: Competitive Landscape

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

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

Key Players

• NBE-Therapeutics
• ImmunoGen, Inc.
• Seagen Inc.
• ADC Therapeutics
• Mythic Therapeutics
• Sutro Biopharma
• Merck KGaA
• Sorrento Therapeutics, Inc.
• Peak Bio
• Regeneron Pharmaceuticals
• Asana BioSciences
• Tanabe Research Laboratories USA
• OBI Pharma
• Sanofi
• Navrogen, Inc.

Key Products

• Zynlonta
• Ladiratuzumab Vedotin
• NBE-002
• IMGN151
• Camidanlumab tesirine
• ADCT-602
• ADCT-901
• ADCT-701
• ADCT-212
• ADCT-601
• IMGN-632
• IMGC 936
• IMGN-151
• MYTX-011
• M1231
• STI-6129
• Torpedo
• BCMA ADC
• REGN5093-M114
• ASN004
• TR 1801 ADC
• OBI 999
• R 992
• NAV-001