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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
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.
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.
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.
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.
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.
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.
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,
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

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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