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With the approval of many antibody-drug conjugation (ADC) drugs around the world since 2019, conjugate drugs have developed into one of the hottest tracks in the pharmaceutical industry. Not only the research and development of traditional ADCs continues to be hot, but various new drug conjugates (NDCs) are also blooming. In this article, we make statistics on the research and development pipeline of new conjugate drugs, in addition to ADC, including PDC, ARC, APC, AExC, AEC, ABC, ISAC, ACC, AOC, and ADeC. The specific research numbers are as follows:
| Drug Conjugates | Preclinical | Phase I | Phase I I | Phase I I I | Apply for Listing | Number of Listings | Total Number of Global Pipelines |
| ADC | 328 | 58 | 39 | 8 | 0 | 12 | 445 |
| PDC | 17 | 3 | 7 | 2 | 0 | 0 | 29 |
| ARC | 2 | 3 | 0 | 1 | 0 | 1 | 7 |
| APC | 4 | 0 | 0 | 0 | 1 | 0 | 5 |
| AExC | 16 | 4 | 4 | 0 | 0 | 2 | 26 |
| ABC | - | - | - | 1 | - | - | - |
| AEC | 1 | 0 | 1 | 0 | 0 | 0 | 2 |
| ISAC | 17 | 2 | 4 | 1 | 0 | 0 | 24 |
| ACC | 1 | 0 | 0 | 1 | 0 | 0 | 2 |
| AOC | 3 | 0 | 1 | 0 | 0 | 0 | 4 |
| ADeC | 5 | 0 | 0 | 0 | 0 | 0 | 5 |
With advanced development capabilities in the field of ADC, BOC Sciences can provide a comprehensive selection of linkers for conjugated drug development. Linkers play a crucial role in the design of conjugated drugs, as they determine the stability, release kinetics, and overall efficacy of the conjugate. BOC Sciences offers a variety of linkers, including cleavable linkers, non-cleavable linkers, and pH-sensitive linkers, to accommodate different drug payloads and target antigens. These linkers are designed to be stable in circulation but release cytotoxicity upon internalization by target cancer cells, ensuring maximum therapeutic efficacy while minimizing off-target toxicity.
BOC Sciences offers a wide range of cytotoxic agents, including potent chemotherapy drugs such as maytansinoids, auristatins, and calicheamicin. These cytotoxins are very effective at killing cancer cells and have been used in the development of several FDA-approved ADCs. Our cytotoxins are available in a variety of formats, including unconjugated drugs, drug-linker conjugates and drug-antibody conjugates, to meet the specific needs of different research projects.
| Catalog | Product Name | CAS Number | Category |
| BADC-00780 | Spliceostatin A | 391611-36-2 | ADCs Cytotoxin |
| BADC-00038 | Doxorubicin hydrochloride | 25316-40-9 | ADCs Cytotoxin |
| BADC-00330 | Irofulven | 158440-71-2 | ADCs Cytotoxin |
| BADC-00569 | Cryptophycin 1 | 124689-65-2 | ADCs Cytotoxin |
| BADC-00797 | Distamycin A | 636-47-5 | ADCs Cytotoxin |
| BADC-00153 | Chlorotoxin | 163515-35-3 | ADCs Cytotoxin |
| BADC-00831 | Telomestatin | 265114-54-3 | ADCs Cytotoxin |
| BADC-00606 | Deruxtecan | 1599440-13-7 | ADCs Cytotoxin with Linkers |
| BADC-00036 | Triptolide | 38748-32-2 | ADCs Cytotoxin |
| BADC-00179 | Colcemide | 477-30-5 | ADCs Cytotoxin |
Drug conjugates are a promising method of drug delivery that combine the specificity of targeted therapies with the potency of cytotoxic drugs. By conjugating drugs to targeting moieties, researchers can improve a drug's pharmacokinetic properties, enhance its ability to reach its target site, and overcome drug resistance. At present, a variety of new conjugation technology concepts have emerged, including peptide drug conjugates (PDC), small molecule drug conjugates (SMDC), immunostimulatory antibody conjugates (ISAC), antibody-oligonucleotides conjugates (AOC), radionuclide drug conjugates (RDC), etc.
Fig. 1. Illustration and types of drug conjugates (Int J Mol Sci. 2023, 24(1): 829).
PDC (peptide-drug conjugate) is composed of linker, homing peptide and cytotoxic payload. Targeting peptides can specifically target protein receptors overexpressed on the surface of tumor cells to deliver cytotoxins to induce tumor cell apoptosis. Compared with the current ADC drugs, PDC drugs have the characteristics of small molecular weight, strong tumor penetration, low immunogenicity, large-scale synthesis by solid-phase synthesis, low production cost, and relatively good pharmacokinetics. From the perspective of the R&D pipeline, the current highest R&D stage in this field is clinical phase III. The representative drugs are paclitaxel trevatide (SNG1005) and zoptarelin doxorubicin (AEZS-108). SNG1005 is a peptide drug conjugate that penetrates the blood and brain. It is obtained by conjugating paclitaxel with an amino acid short peptide. It can specifically deliver paclitaxel to the brain. Phase II clinical results show that SNG1005 has shown positive clinical therapeutic effects in the treatment of breast cancer with leptomal metastasis and recurrent breast cancer with brain parenchymal metastasis. AEZS-108, a combination of a luteinizing hormone-releasing hormone (LHRH) agonist and doxorubicin, is currently in clinical trials in patients with castration-resistant prostate cancer.
Representative drugs of ARC (antibody-radionuclide conjugate) include Ibritumomab tiuxetan (Zevalin) developed by Japan's IDEC Company. After Zevalin injects the anti-CD20 monoclonal antibody carrying the radionuclide into the patient, it will bind to mature B cells and B cell tumor cells expressing CD20, and kill these cells through the radiation released by the radionuclide. In addition, mirvetuximab soravtansine (MIRV), jointly developed by ImmunoGen and Sino-US Huadong, binds to the folate receptor (FRα) and is transferred to the interior of cells. The cytotoxic molecule DM4 it carries can inhibit the mitosis of cancer cells and achieve the effect of treating cancer. MIRV was developed to treat platinum-resistant ovarian cancer with high expression of FRα and is First-in-class.
The representative drug of APC (antibody-photosensitizer conjugate) is cetuximab sarotalocan (Akalux) developed by Rakuten Medical, which received accelerated approval from PMDA in September 2020. Akalux is an antibody-drug conjugate composed of cetuximab and IRDye700DX that targets the epidermal growth factor receptor (EGFR). It is used for the treatment of unresectable locally advanced or locally recurrent head and neck cancer and is the world's first approved batch of photoimmunotherapy drugs.
The representative drug of AExC (antibody-exotoxin conjugate) is AstraZeneca's moxetumomab pasudotox, which is a conjugate of a CD22 monoclonal antibody and Pseudomonas exotoxin (PE38). It has been approved by the FDA for the treatment of hairy cell leukemia (HCL). Another approved representative drug is loncastuximab tesirine developed by ADC Therapeutics, which consists of a humanized anti-CD19 antibody and pyrrolobenzodiazepine dimeric toxin SG3199. It was approved by the FDA in April 2021 for the treatment of diffuse large B-cell lymphoma.
The representative drug of ABC (Antibody-Biopolymer Conjugate) is KSI-301 developed by Kodiak Sciences. KSI-301 is a novel anti-VEGF biologic developed based on the company's proprietary ABC technology platform. It is designed to increase the duration of drug retention within eye tissue, thereby improving efficacy and reducing the number of injections, and is currently being developed to treat retinal vascular disease and prevent vision loss in patients with diabetic eye disease.
The representative drug of AEC (antibody-enzyme conjugate) is L-DOS47 developed by Helix BioPharma targeting CEACAM6 (overexpressed in various epithelial malignant tumors). L-DOS47 is the first targeted therapeutic immunoconjugate developed based on the company's DOS47 technology, which includes a highly specialized camel-derived single domain antibody in which a urease component enzymatically converts naturally occurring urea to ammonia. It is currently being developed to treat non-small cell lung cancer (NSCLC) and pancreatic cancer.
The representative drug of ISAC (immune stimulating antibody conjugate) is BDC-1001 developed by Bolt Biotherapeutics. It consists of an anti-HER-2 trastuzumab biosimilar conjugated to a TLR 7/8 dual agonist through a non-cleavable linker and is used to treat HER2-positive solid tumors. In December 2022, Bolt Therapeutics announced the Phase 1/2 clinical data of BDC-1001 at the ESMO meeting. Among 40 evaluable patients, 1 patient had partial response and 12 patients had stable disease. The overall response rate (ORR) was only 2.5%, and the disease control rate (DCR) was 32.5%. The performance was not satisfactory.
The representative drug of ACC (antibody-cell conjugate) is based on ACE1702 developed by Acepodia Company and is currently in the Phase I clinical stage. In both in vivo and in vitro studies, ACE1702 showed enhanced tumor cell killing activity. At the same time, ACE1702 also maintained good safety in GLP toxicology studies.
The representative drug of AOC (antibody-oligonucleotide conjugate) is AOC-1001 developed by Avidity Biosciences. Avidity Biosciences is a pioneer in the development of AOC, which combines the tissue selectivity of monoclonal antibodies and the accuracy of oligonucleotide-based therapeutic methods, thus overcoming the obstacles that hinder the transmission of oligonucleotides and the genetic drivers of targeted diseases. It is used to treat rare muscle disorders and other serious conditions. AOC-1001, the first to enter clinical practice, consists of three parts: a full-length monoclonal antibody targeting transferrin receptor 1 (TfR1), a linker, and siRNA targeting DMPK mRNA. The indication is myotonic dystrophy type 1 (DM1).
ADeC (antibody-degrader conjugate) is currently in the early development stage. Its technical principle is to use protein degradation agents as payloads, which combines the tumor specificity of ADC and the applicability of low expression under the amount of PROTAC molecular catalyst, and is used to treat solid tumors. The representative drug is ORM-5029 developed by Orum Therapeutics.
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