The document summarizes several bispecific antibody-drug conjugates (ADCs) currently in clinical or preclinical development. It describes ZW-49 and M1231, which are HER2/HER2 and MUC1/EGFR bispecific ADCs, respectively. It also discusses JSKN003, a HER2 bispecific ADC, and BL-B01D1, an EGFR/HER3 bispecific ADC. The document notes that bispecific ADCs have potential advantages over monoclonal ADCs but development is challenging and few are currently beyond early stages of research.
Global antibody-drug-conjugate-adc-clinical-trial-reviewEchoHan4
As innovative next-generation immunotherapeutic agents, antibody-drug conjugates (ADCs) are being developed worldwide as a major strategy to combat cancer and other immunological disorders. With the combination of a monoclonal antibody and extremely toxic chemical payloads, these biomacromolecule “warheads” are by far one of the most powerful weapons in the immunotherapy arsenal, bearing the hope as “the beginning of the end” to the battle against cancer. https://www.creative-biolabs.com/adc/druglnk-custom-synthesis.htm
With the combination of a monoclonal antibody and extremely toxic chemical payloads, these biomacromolecule “warheads” are by far one of the most powerful weapons in the immunotherapy arsenal, bearing the hope as “the beginning of the end” to the battle against cancer. https://www.creative-biolabs.com/adc/platform.htm
A Comprehensive Guide to ADC Payload Classes.pdfDoriaFang
ADC payloads are critical components of the ADC structure, and their selection and design are crucial for achieving optimal therapeutic efficacy and minimizing toxicity.
ADC Drugs For Non-small Cell Lung Cancer.pdfDoriaFang
Despite the rapid progress of targeted therapy in the field of NSCLC (non-small cell lung cancer), there are still unmet needs. This article summarizes the latest progress in the targeted therapy of Her2, Her3 and Trop-2 in NSCLC.
Global antibody-drug-conjugate-adc-clinical-trial-reviewEchoHan4
As innovative next-generation immunotherapeutic agents, antibody-drug conjugates (ADCs) are being developed worldwide as a major strategy to combat cancer and other immunological disorders. With the combination of a monoclonal antibody and extremely toxic chemical payloads, these biomacromolecule “warheads” are by far one of the most powerful weapons in the immunotherapy arsenal, bearing the hope as “the beginning of the end” to the battle against cancer. https://www.creative-biolabs.com/adc/druglnk-custom-synthesis.htm
With the combination of a monoclonal antibody and extremely toxic chemical payloads, these biomacromolecule “warheads” are by far one of the most powerful weapons in the immunotherapy arsenal, bearing the hope as “the beginning of the end” to the battle against cancer. https://www.creative-biolabs.com/adc/platform.htm
A Comprehensive Guide to ADC Payload Classes.pdfDoriaFang
ADC payloads are critical components of the ADC structure, and their selection and design are crucial for achieving optimal therapeutic efficacy and minimizing toxicity.
ADC Drugs For Non-small Cell Lung Cancer.pdfDoriaFang
Despite the rapid progress of targeted therapy in the field of NSCLC (non-small cell lung cancer), there are still unmet needs. This article summarizes the latest progress in the targeted therapy of Her2, Her3 and Trop-2 in NSCLC.
PROTAC Technology: An Effective Targeted Protein Degrader.pdfDoriaFang
PROTACs are heterofunctional small molecules consisting of two ligands linked by an appropriate linker: one ligand recruits and binds the protein of interest (POI), while the other recruits and binds the E3 ubiquitin ligase.
Antibody drug conjugates (ADCs) are undoubtedly one of the hottest research areas in recent years. To date, there are 15 approved ADCs in the world, of which 13 have been approved by the FDA, one in China (Disitamab Vedotin) and one in Japan (Akalux).
Similar to HER2, Trop-2 is a new hot target for research. Trodelvy has been one of the products receiving much attention in recent years, and Dato-DXd from AstraZeneca/Daiichi Sankyo is also advancing rapidly.
Summary of ADC Targets For Solid Tumors & Hematological Tumors.pdfDoriaFang
Currently, popular targets include CD family, BCMA, HER2, TROP2, Tissue factor, Nectin-4, FRα, EGFR, etc. Here, we briefly introduce ADC targets in solid tumors and hematological tumors.
ADC’s - What Everyone with MBC Should Know about Antibody Drug Conjugatesbkling
Antibody drug conjugates (ADC’s), a novel class of anticancer agents, have been around for decades but recently great strides have been made in metastatic breast cancer. Next generation ADC’s, sometimes referred to as ' Trojan Horses' have shown promising efficacy in all subtypes of MBC. Join Dr. Erika Hamilton, Director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute, and partner with Tennessee Oncology PLCC, as she presents an overview of ADC’s, biomarkers and clinical mapping, current treatment options, as well as the promising trials to keep an eye on. There will be time for your questions throughout the presentation.
Trophoblast Glycoprotein (TPGB5T4) A New Target For ADC Drugs.pdfDoriaFang
The more popular targets in ADC drugs include HER2, TROP2, EGFR, CLDN18.2, c-Met, CD19, PSMA, Muc1, BCMA and PDL1. Here we will introduce a new ADC target trophoblast glycoprotein (TPBG).
Antibody drug conjugates for cancer therapy - prospects and challenges htpDoriaFang
Antibody-drug conjugates (ADCs) are a rapidly evolving class of anticancer therapeutics consisting of antibodies attached to potent cytotoxic drugs via chemical linkers. What're the prospects and challenges of Antibody-Drug Conjugates for cancer therapy?
Peptide drug conjugates (pd cs) new generation of targeted cancer treatmentDoriaFang
As a new generation of targeted cancer treatment, the well-designed PDC not only retains the advantages of traditional drug delivery, but also increases the penetration of tumor drugs and reduces the toxicity to liver and kidney.
Summary of Approved HER2 ADCs on The Market & in Clinical Trials.pdfDoriaFang
Studies have shown that human epidermal growth factor receptor-2 (HER2) is overexpressed in many tumors and is one of the most common target antigens for ADCs.
Immunotherapeutic drugs can be broadly classified into four types: checkpoint inhibitors, cytokines, monoclonal antibodies, and vaccines. However, immunotherapeutic drugs still have some problems, such as off-target side effects and poor pharmacokinetics.
Peptide Drug Conjugates (PDCs) Novel Targeted Therapeutics For Cancer.pdfDoriaFang
Peptide-drug conjugates (PDCs) are the next generation of targeted therapies after ADCs. PDCs has been developed as targeted therapeutic candidates for cancer, COVID-19, metabolic diseases, etc.
Cyclic Peptides Current Status & Future Prospects.pdfDoriaFang
Researchers have made unremitting efforts to optimize peptides in order to improve the bioavailability of peptide drugs. Cyclization of peptides is one of the methods to optimize peptides. Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics.
Antibody–Oligonucleotide Conjugates (AOCs) in Clinical Trials.pdfDoriaFang
Summary of Antibody–Oligonucleotide Conjugates(AOCs) in Clinical Trials, including products from Avidity Biosciences, Dyne Therapeutics, Tallac Therapeutics and Denali Therapeutics.
Alzheimer's Disease Drug Development Aducanumab, Lecanemab & Donanemab.pdfDoriaFang
Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive and behavioral impairment. Here we introduce the development of AD drugs (Aducanumab, Lecanemab & Donanemab).
More Related Content
Similar to Bispecific Antibody-drug Conjugate Drugs In Clinical or Preclinical.pdf
PROTAC Technology: An Effective Targeted Protein Degrader.pdfDoriaFang
PROTACs are heterofunctional small molecules consisting of two ligands linked by an appropriate linker: one ligand recruits and binds the protein of interest (POI), while the other recruits and binds the E3 ubiquitin ligase.
Antibody drug conjugates (ADCs) are undoubtedly one of the hottest research areas in recent years. To date, there are 15 approved ADCs in the world, of which 13 have been approved by the FDA, one in China (Disitamab Vedotin) and one in Japan (Akalux).
Similar to HER2, Trop-2 is a new hot target for research. Trodelvy has been one of the products receiving much attention in recent years, and Dato-DXd from AstraZeneca/Daiichi Sankyo is also advancing rapidly.
Summary of ADC Targets For Solid Tumors & Hematological Tumors.pdfDoriaFang
Currently, popular targets include CD family, BCMA, HER2, TROP2, Tissue factor, Nectin-4, FRα, EGFR, etc. Here, we briefly introduce ADC targets in solid tumors and hematological tumors.
ADC’s - What Everyone with MBC Should Know about Antibody Drug Conjugatesbkling
Antibody drug conjugates (ADC’s), a novel class of anticancer agents, have been around for decades but recently great strides have been made in metastatic breast cancer. Next generation ADC’s, sometimes referred to as ' Trojan Horses' have shown promising efficacy in all subtypes of MBC. Join Dr. Erika Hamilton, Director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute, and partner with Tennessee Oncology PLCC, as she presents an overview of ADC’s, biomarkers and clinical mapping, current treatment options, as well as the promising trials to keep an eye on. There will be time for your questions throughout the presentation.
Trophoblast Glycoprotein (TPGB5T4) A New Target For ADC Drugs.pdfDoriaFang
The more popular targets in ADC drugs include HER2, TROP2, EGFR, CLDN18.2, c-Met, CD19, PSMA, Muc1, BCMA and PDL1. Here we will introduce a new ADC target trophoblast glycoprotein (TPBG).
Antibody drug conjugates for cancer therapy - prospects and challenges htpDoriaFang
Antibody-drug conjugates (ADCs) are a rapidly evolving class of anticancer therapeutics consisting of antibodies attached to potent cytotoxic drugs via chemical linkers. What're the prospects and challenges of Antibody-Drug Conjugates for cancer therapy?
Peptide drug conjugates (pd cs) new generation of targeted cancer treatmentDoriaFang
As a new generation of targeted cancer treatment, the well-designed PDC not only retains the advantages of traditional drug delivery, but also increases the penetration of tumor drugs and reduces the toxicity to liver and kidney.
Summary of Approved HER2 ADCs on The Market & in Clinical Trials.pdfDoriaFang
Studies have shown that human epidermal growth factor receptor-2 (HER2) is overexpressed in many tumors and is one of the most common target antigens for ADCs.
Immunotherapeutic drugs can be broadly classified into four types: checkpoint inhibitors, cytokines, monoclonal antibodies, and vaccines. However, immunotherapeutic drugs still have some problems, such as off-target side effects and poor pharmacokinetics.
Peptide Drug Conjugates (PDCs) Novel Targeted Therapeutics For Cancer.pdfDoriaFang
Peptide-drug conjugates (PDCs) are the next generation of targeted therapies after ADCs. PDCs has been developed as targeted therapeutic candidates for cancer, COVID-19, metabolic diseases, etc.
Cyclic Peptides Current Status & Future Prospects.pdfDoriaFang
Researchers have made unremitting efforts to optimize peptides in order to improve the bioavailability of peptide drugs. Cyclization of peptides is one of the methods to optimize peptides. Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics.
Antibody–Oligonucleotide Conjugates (AOCs) in Clinical Trials.pdfDoriaFang
Summary of Antibody–Oligonucleotide Conjugates(AOCs) in Clinical Trials, including products from Avidity Biosciences, Dyne Therapeutics, Tallac Therapeutics and Denali Therapeutics.
Alzheimer's Disease Drug Development Aducanumab, Lecanemab & Donanemab.pdfDoriaFang
Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive and behavioral impairment. Here we introduce the development of AD drugs (Aducanumab, Lecanemab & Donanemab).
Summary of Targeted Protein Degradation in Clinical Trials.pdfDoriaFang
Summary of targeted protein degradation, such as PROTAC and molecular glues in clinical trials. PROTAC and molecular glues are the two main modes of TPD technology based on the UPS.
Cleavable Linkers Used In ADC Development.pdfDoriaFang
The linker used in ADC is divided into two types: cleavable linker and non-cleavable linker. This artile mainly introduced the cleavable linkers used in ADC development.
The Role of Four Lipid Components Of LNPs.pdfDoriaFang
LNP consists of four components: ionizable cationic lipids, phospholipids, cholesterol, and PEG lipids. Each component plays a key role in terms of LNP preparations.
DS-8201 (Enhertu) A Potential ADC Drug Targeting HER2.pdfDoriaFang
Enhertu (fam-Trastuzumab deruxtecan-nxki) is a HER2-targeting ADC drug jointly developed by AstraZeneca and Daiichi Sankyo, also known as DS-8201 or T-DXd.
List of New Anti-cancer Drugs Approved By FDA In The First Half of 2023.pdfDoriaFang
What are the new anti-cancer drugs approved in the first half of the year? The new drugs approved covered a variety of solid tumors and blood tumor types.
New Oncology Trends ADCs, Bispecific Antibodies & CAR-T Cell.pdfDoriaFang
Scientists are turning their attention to more innovative therapeutic strategies, such as next-generation ADCs, bispecific antibodies and CAR-T cell therapies, etc. as cancer therapy.
Summary of Treatments for Multiple Myeloma.pdfDoriaFang
Currently, there are a variety of drugs available for multiple myeloma, including traditional cytotoxic drugs, immunomodulatory analogs, proteasome inhibitors, antibody-based drugs and CAR T-cell therapy.
PROTAC Delivery System Recent Research Advances.pdfDoriaFang
The combination of PROTAC and multifunctional delivery systems will open up new research directions in the field of TPD. Here we will introduce the combination of PROTAC and multifunctional delivery systems.
Aptamer-Drug Conjugate (ApDC) Current Research Progress.pdfDoriaFang
ADCs, PDCs, ISACs, SMDC and Aptamer-Drug Conjugate (ApDC) are the conjugated drugs currently being developed. Here we will introduce the current research progress and challenges of ApDC.
FRα Targeting ADCs for Ovarian cancer.pdfDoriaFang
This article introduces FRα targets and FRα ADCs in clinical trials. There is only one FRα targeting ADC for ovarian cancer - mirvetuximab soravtansine-gynx (Elahere) and a few in clinical trials.
Maytansinoids as Payloads of ADCs DM1, DM4.pdfDoriaFang
ADCs with maytansine derivatives as cytotoxic agents have been highly favored by researchers and a series of breakthroughs have been achieved. DM1, DM4 are maytansinoids as ADC payloads.
VAT Registration Outlined In UAE: Benefits and Requirementsuae taxgpt
Vat Registration is a legal obligation for businesses meeting the threshold requirement, helping companies avoid fines and ramifications. Contact now!
https://viralsocialtrends.com/vat-registration-outlined-in-uae/
The world of search engine optimization (SEO) is buzzing with discussions after Google confirmed that around 2,500 leaked internal documents related to its Search feature are indeed authentic. The revelation has sparked significant concerns within the SEO community. The leaked documents were initially reported by SEO experts Rand Fishkin and Mike King, igniting widespread analysis and discourse. For More Info:- https://news.arihantwebtech.com/search-disrupted-googles-leaked-documents-rock-the-seo-world/
Affordable Stationery Printing Services in Jaipur | Navpack n PrintNavpack & Print
Looking for professional printing services in Jaipur? Navpack n Print offers high-quality and affordable stationery printing for all your business needs. Stand out with custom stationery designs and fast turnaround times. Contact us today for a quote!
RMD24 | Debunking the non-endemic revenue myth Marvin Vacquier Droop | First ...BBPMedia1
Marvin neemt je in deze presentatie mee in de voordelen van non-endemic advertising op retail media netwerken. Hij brengt ook de uitdagingen in beeld die de markt op dit moment heeft op het gebied van retail media voor niet-leveranciers.
Retail media wordt gezien als het nieuwe advertising-medium en ook mediabureaus richten massaal retail media-afdelingen op. Merken die niet in de betreffende winkel liggen staan ook nog niet in de rij om op de retail media netwerken te adverteren. Marvin belicht de uitdagingen die er zijn om echt aansluiting te vinden op die markt van non-endemic advertising.
Cracking the Workplace Discipline Code Main.pptxWorkforce Group
Cultivating and maintaining discipline within teams is a critical differentiator for successful organisations.
Forward-thinking leaders and business managers understand the impact that discipline has on organisational success. A disciplined workforce operates with clarity, focus, and a shared understanding of expectations, ultimately driving better results, optimising productivity, and facilitating seamless collaboration.
Although discipline is not a one-size-fits-all approach, it can help create a work environment that encourages personal growth and accountability rather than solely relying on punitive measures.
In this deck, you will learn the significance of workplace discipline for organisational success. You’ll also learn
• Four (4) workplace discipline methods you should consider
• The best and most practical approach to implementing workplace discipline.
• Three (3) key tips to maintain a disciplined workplace.
Kseniya Leshchenko: Shared development support service model as the way to ma...Lviv Startup Club
Kseniya Leshchenko: Shared development support service model as the way to make small projects with small budgets profitable for the company (UA)
Kyiv PMDay 2024 Summer
Website – www.pmday.org
Youtube – https://www.youtube.com/startuplviv
FB – https://www.facebook.com/pmdayconference
[Note: This is a partial preview. To download this presentation, visit:
https://www.oeconsulting.com.sg/training-presentations]
Sustainability has become an increasingly critical topic as the world recognizes the need to protect our planet and its resources for future generations. Sustainability means meeting our current needs without compromising the ability of future generations to meet theirs. It involves long-term planning and consideration of the consequences of our actions. The goal is to create strategies that ensure the long-term viability of People, Planet, and Profit.
Leading companies such as Nike, Toyota, and Siemens are prioritizing sustainable innovation in their business models, setting an example for others to follow. In this Sustainability training presentation, you will learn key concepts, principles, and practices of sustainability applicable across industries. This training aims to create awareness and educate employees, senior executives, consultants, and other key stakeholders, including investors, policymakers, and supply chain partners, on the importance and implementation of sustainability.
LEARNING OBJECTIVES
1. Develop a comprehensive understanding of the fundamental principles and concepts that form the foundation of sustainability within corporate environments.
2. Explore the sustainability implementation model, focusing on effective measures and reporting strategies to track and communicate sustainability efforts.
3. Identify and define best practices and critical success factors essential for achieving sustainability goals within organizations.
CONTENTS
1. Introduction and Key Concepts of Sustainability
2. Principles and Practices of Sustainability
3. Measures and Reporting in Sustainability
4. Sustainability Implementation & Best Practices
To download the complete presentation, visit: https://www.oeconsulting.com.sg/training-presentations
What are the main advantages of using HR recruiter services.pdfHumanResourceDimensi1
HR recruiter services offer top talents to companies according to their specific needs. They handle all recruitment tasks from job posting to onboarding and help companies concentrate on their business growth. With their expertise and years of experience, they streamline the hiring process and save time and resources for the company.
Implicitly or explicitly all competing businesses employ a strategy to select a mix
of marketing resources. Formulating such competitive strategies fundamentally
involves recognizing relationships between elements of the marketing mix (e.g.,
price and product quality), as well as assessing competitive and market conditions
(i.e., industry structure in the language of economics).
RMD24 | Retail media: hoe zet je dit in als je geen AH of Unilever bent? Heid...BBPMedia1
Grote partijen zijn al een tijdje onderweg met retail media. Ondertussen worden in dit domein ook de kansen zichtbaar voor andere spelers in de markt. Maar met die kansen ontstaan ook vragen: Zelf retail media worden of erop adverteren? In welke fase van de funnel past het en hoe integreer je het in een mediaplan? Wat is nu precies het verschil met marketplaces en Programmatic ads? In dit half uur beslechten we de dilemma's en krijg je antwoorden op wanneer het voor jou tijd is om de volgende stap te zetten.
Premium MEAN Stack Development Solutions for Modern BusinessesSynapseIndia
Stay ahead of the curve with our premium MEAN Stack Development Solutions. Our expert developers utilize MongoDB, Express.js, AngularJS, and Node.js to create modern and responsive web applications. Trust us for cutting-edge solutions that drive your business growth and success.
Know more: https://www.synapseindia.com/technology/mean-stack-development-company.html
Putting the SPARK into Virtual Training.pptxCynthia Clay
This 60-minute webinar, sponsored by Adobe, was delivered for the Training Mag Network. It explored the five elements of SPARK: Storytelling, Purpose, Action, Relationships, and Kudos. Knowing how to tell a well-structured story is key to building long-term memory. Stating a clear purpose that doesn't take away from the discovery learning process is critical. Ensuring that people move from theory to practical application is imperative. Creating strong social learning is the key to commitment and engagement. Validating and affirming participants' comments is the way to create a positive learning environment.
Bispecific Antibody-drug Conjugate Drugs In Clinical or Preclinical.pdf
1. Huateng Pharma https://us.huatengsci.com
Bispecific Antibody-drug Conjugate Drugs In
Clinical or Preclinical
Bispecific Antibody-drug Coniugate (ADC) is a new concept. Compared
with monoclonal antibody, it can target tumor cells more specifically through
bispecific antibody, overcome drug resistance and reduce the side effects of
drugs. In addition, the synergic endocytosis of the two targets was promoted
through cross-linking, which not only improved the efficiency of toxin entering
tumor cells, but also further inhibited tumor cell growth signals by reducing the
expression of receptor proteins on the cell membrane, so as to achieve better
therapeutic effects.
Bispecific antibodies, as antibodies that can simultaneously bind to two
different antigens, have more room to play in terms of their mechanism of
action. Bispecific antibodies have achieved success in hematological tumors.
At present, 7 types of bispecific antibodies have been approved for
marketing, including blinatumomab targeting CD19/CD3,emicizumab targeting
FIXa/FX, mosunetuzumab targeting CD20/CD3 and so on (as below table).
And there are many other bispecific antibodies targeting against hematological
tumors have achieved good results in clinical practice.
ADC drugs, as a drug of targeted delivery of poison, have achieved great
success in the treatment of solid tumors. The mechanism of action is different
from bispecific antibodies drugs that kill tumors through the body's immune
system, ADC mainly inhibits and kills tumor cells through its payload, but
the current ADC drugs are also unable to reach the optimal therapeutic
window due to toxicity problems. So what is the effect of the combination of
bispecific antibodies and ADC, and can it enhance its strengths and avoid its
weaknesses? According to the current preclinical data, partial bispecific ADC
not only has better efficacy than naked antibody, but also has good safety, but
2. Huateng Pharma https://us.huatengsci.com
its final effect still needs to be verified in the clinic. In this article, we will
introduce the preclinical data of some currently known bispecific ADC
drugs in clinical or preclinical.
Since the field of bispecific ADC is still in the early stage of exploration, there
are currently few products under research. Perhaps because the mature target
HER2 has been fully verified in various therapies, the current bispecific ADC
drugs under research are mainly HER2 bispecific ADC, whose representative
products include ZW49, M1231, JSKN003 and so on.
ZW-49
Currently, the world's fastest-growing HER2-specific antibody ADC drug is
ZW49 from Zymeworks. It can specifically bind two non-overlapping epitopes
of the HER2 receptor (ECD4/trastuzumab and ECD2/pertuzumab) at the same
time. The bispecific ADC is based on ZW25 and is coupled to Auristatin toxin A
by protease cleavage linker. In the preclinical NHP animal model, the highest
tolerated dose of the double antibody ADC reached 18mg/kg.
The drug is a modification of the bispecific ADC ZW25 (a new type of
humanized double antibody that can simultaneously bind to two
non-overlapping epitopes of HER2), so it has various advantages of ZW25,
such as effectively aggregating HER2 receptors on the cell surface and
enhancing HER2 internalization and downregulation. The antibody part adopts
an antibody structure similar to that of ZW25. Through Zymelink technology,
the linked payload is a microtubule inhibitor derived from the chemotherapy
drug Auristatin agent. Since ZW49 can simultaneously bind to the binding site
of pertuzumab and trastuzumab, theoretically, ZW49 can play a good
therapeutic effect for patients resistant to new ADC drugs such as
trastuzumab, pertuzumab, and even TDM-1. In mouse tumor models, ZW49
showed stronger antitumor activity than T-DM1 and DS-8201.
3. Huateng Pharma https://us.huatengsci.com
In preclinical animal models, ZW-49 can effectively kill tumors with medium
and high expression of HER2, and it can significantly prolong the survival time
and probability of survival of animals compared with positive control drugs. The
drug is currently in Phase I clinical trials, and relevant data has not yet been
disclosed.
M1231
M1231 is a MUCI/EGFR bispecific ADC jointly developed by Sutro and Merck.
The bispecific ADC adopts the Sutro non-natural amino acid site-specific
coupling technology, and prevents the mismatch of the two heavy chains
through Merck's SEED bispecific antibody technology platform. The antibody
targeting MUCI is scFv, while the antibody targeting EGFR is Fab. This design
does not have the problem of light chain mismatching in the traditional
double-antibody design. In the production, the expression of the antibody was
adopted by Sutro's cell-free system XpressCF, and non-natural amino acids
were inserted at a fixed point during the production process to facilitate the
site-specific coupling of subsequent bispecific antibodies. On the toxin side,
the microtubule inhibitor hemiasterlin is used and the antibody is coupled to
the toxin via a lysable Val-Cit linker.
4. Huateng Pharma https://us.huatengsci.com
Merck chose MUCI/EGFR as the target because relevant studies have shown
that MUCI/EGFR are co-expressed in a variety of tumor cells, such as
non-small cell lung cancer, esophageal squamous cell carcinoma,
triple-negative breast cancer, etc., but the expression level in normal tissues is
very low, so theoretically it can reduce On-target toxicity and improve the drug
window. In addition, the study showed that the antibody binds to two antigens
on the surface of the tumor at the same time, causing the antibody to
endocytosis rapidly and releasing a response toxin to inhibit the growth of the
tumor cells. Clinical data are not yet available.
In the preclinical animal model of PDX, 8mg/kg single dose treatment of mice
can inhibit the growth of tumors and even clear tumors to a certain extent, and
the drug has now entered the clinic.
5. Huateng Pharma https://us.huatengsci.com
JSKN003
JSKN003 is a bispecific ADC targeting HER2 developed by Alphamab
Oncology. The bispecific antibody is modified and designed on the basis of
KN026. It is similar to ZW-49 and targets two different epitopes of HER
( ECD4/trastuzumab and ECD2/pertuzumab). JSKN003 utilizes specific site
conjugation with a DAR value of 3-4. Its efficacy is comparable to that of
Daiichi Sankyo’s ENHERTU (DS- 8201a) quite.
Preclinical studies have shown that JSKN003 has better serum stability and
stronger bystander killing effect than similar drugs. It showed a favorable
safety profile in both HER2 high and low expression cells (CDX+PDX model).
JSKN003 is currently undergoing phase I clinical research in Australia. In
addition to the development of bispecific ADC drugs, Alphamab Oncology is
also currently deploying drugs related to bispecific antibodies coupling
modulators.
BL-B01D1
BL-B01D1 is a bispecific ADC drug targeting EGFR and Her3 developed by
Baili Pharmaceuticals. The antibody part is SI-B001, which is an EGFR×HER3
double antibody developed by Sichuan Biokin Pharmaceutical Co.,Ltd., which
can block the binding of EGF and EGFR, NRG1 and HER3, inhibit the
formation of EGFR homologous dimer and the heterodimer of EGFR and
HER3 and the activation of downstream signaling pathway, thus inhibiting the
proliferation and metastasis of tumor cells. The small-molecule toxin of
BL-B01D1 is the camphin analogue ED04 developed by the company, and the
Payload is an Ac connector with independent intellectual property rights.
Compared with the common Mc connector, the Ac connector has better
stability, which can effectively avoid the shedding of drug molecules and
ensure the stability of toxin circulation in the body.
With this structural design, BL-B01D1 can simultaneously bind EGFR and
HER3 on tumor cells to achieve simultaneous blocking of two tumor-related
targets. On the other hand, small molecular toxins enter tumor cells through
endocytosis and have stronger tumor killing activity.
In terms of the mechanism of action, BL-B01D1 can not only block the relevant
binding of EGFR, HER3 and ligand at the same time, but also enter the cell
through endocytosis after binding with EGFR and HER3, and release small
molecule toxin ED04 by hydrolysis enzyme, which prevents DNA replication
and RNA synthesis of tumor cells and destroys DNA structure. So as to further
kill tumor cells, the drug has entered the clinic in China.
6. Huateng Pharma https://us.huatengsci.com
REGN5093-M114
REGN5093-M114 is a bispecific ADC drug targeting two different epitopes of
MET developed by Regenron. The antibody is a 1+1 asymmetric bispecific
antibody. The antibody is combined with the toxin M24 (maytansine derivative)
through the M114 linker connection, the DAR value is around 3.2. It can
simultaneously bind two different epitopes of MET, and can effectively block
the binding of HGF and MET, thereby preventing the activation of related
pathways. In addition, after the antibody binds to the MET on the surface of
tumor cells, the 2+2 complex formed by the antibody and MET can be
internalized, enter the tumor cells and be degraded in the lysosome, thus
reducing the expression of MET on the cell surface through recycling. In
addition, the cleavable linker in REGN5093-M114 is cleaved in lysosomes to
release M24 toxin and inhibit tumor growth by acting on tubulin.
7. Huateng Pharma https://us.huatengsci.com
Preclinical studies have shown that REGN5093-M114 is not only effective
against conventional tumors with high MET expression, but also has good
efficacy against a variety of tumors with natural or acquired resistance. In
terms of safety, REGN5093-M114 has shown good safety and tolerability in
large animal experiments. REGN5093-M114 is currently in Phase I/II clinical
studies.
CBP-1008
CBP-1008 is a bispecific ADC targeting folate receptor (FRα) and TRPV6 (a
calcium ion channel protein) receptor developed by Coherent Biopharma.
Among them, FRα is highly expressed in tumor types such as ovarian cancer
and breast cancer. TRPV6 is highly expressed in tumor types such as breast
cancer and pancreatic cancer. Previously, CBP-1008 has achieved
encouraging efficacy results in a phase 1b clinical trial for the treatment of
patients with advanced recurrent ovarian cancer for which no drugs are
available. A Phase II clinical trial is currently underway in target-enriched,
advanced recurrent ovarian cancer patients.
YH012
Biocytogen's bispecific ADC YH is constructed on its RenLiteTM bispecific
antibody platform. RenLiteTM uses the common light chain method to prevent
the mismatch of the light chain of the bispecific antibody, and uses
Knob-In-Hole to prevent the mismatch of the heavy chain of the antibody. This
platform can realize the production of high-purity bispecific antibodies. On this
basis, it uses interchain cysteine for coupling, the linker is a cleavable
dipeptide VC (valine-citrulline), and the toxin is MMAE.
8. Huateng Pharma https://us.huatengsci.com
In NCI-N87 tumor cells, bispecific ADC YH012 that target HER2/TROP2 can
be rapidly internalized by tumor cells, and its internalization efficiency is higher
than that of single-target control ADC drugs.
In the in vivo model, bispecific ADC YH012 can effectively inhibit the growth of
tumor cells, which is better than monoclonal antibodies conjugated to the same
toxin in terms of efficacy, and better than higher doses of bispecific antibodies
and naked antibodies.
Conclusion
In the future, bispecific ADCs with multiple advantages will undoubtedly
become a new hotspot in the development of innovative drugs. However, the
bispecific antibody is more complicated, and its efficacy is related to the target
combination and structure of the antibody, as well as the affinity of the two
antibodies. The same is true for ADC, whose efficacy is related to antibodies,
9. Huateng Pharma https://us.huatengsci.com
linkers and toxins. Therefore, the research and development of bispecific ADC
will be more complicated, and requires an in-depth understanding of the
mechanism of action of bispecific antibody and the principle of ADC.
Due to technical difficulties, the field of bispecific ADC drugs are still in the
early stage of exploration. According to the current data, there are not many
bispecific ADC drugs under research, and most of them are in clinical phase
I/II or preclinical stage. The main reason is that there are few antibody
backbone molecules that can be used for the construction of double antibodies,
and the targets are very concentrated. Only a few good antibody molecules
are available at several targets such as HER2, HER3, EGFR, MUC1, etc., and
there is a lack of sufficient skeleton for the rapid construction of stably
expressed bispecific ADC molecules. However, this does not prevent the
bispecific ADC is still a promising and promising field.
As a leading PEG supplier, Huateng Pharma supplies high-quality PEG
derivatives, PEG raw materials and ADC linkers to empower our customer's
advanced research. We are committed to promoting the progress of your ADC
and PDC discovery and development projects.
References:
[1].https://ir.zymeworks.com/news-releases/news-release-details/zymeworks-advances-h
er2-bispecific-antibody-drug-conjugate-zw49
[2]. Prospectus for listing on the Science and Technology Innovation Board of Baili
Tianheng. Retrieved Dec30, 2022,
from https://pdf.dfcfw.com/pdf/H2_AN202212291581494831_1.pdf?1672342025000.pdf;
[3]. A phase Ia/Ib study of CBP-1008, a bispecific ligand drug conjugate, in patients with
advanced solid tumors
[4]. YH012, a Novel Bispecific Anti-HER2 and TROP2 Antibody-Drug Conjugate, Exhibits
Potent Antitumor Efficacy
Related articles:
[1]. Bispecific Antibodies – Fast Growing Therapies
[2]. Directions for Next Generation Antibody-Drug Conjugates
[3]. ADC Linker - Development and Challenges