- New York, United States of America
- October 23, 2024
The novel ADeC—pointing at undruggable targets
Antibody Degraducer Conjugate, also known as ADeC, is currently in its initial stages of research and development. For the treatment of solid tumors, the technological premise behind this approach is to employ protein degraders as the payload. This approach combines the tumor-targeting capabilities of ADC with the appropriateness for low expression at the catalytic quantity offered by PROTAC molecules.
In a press release dated June 23, 2021, Orum Therapeutics said that it has successfully raised $84 million in Series B funding for their "non-druggable" Antibody neoDegrader Conjugate (AnDC) technology platform. When it comes to technology, the AnDCÂ platform can hit so-called "undruggable" targets. It features an antibody-drug conjugate (ADC) that specifically targets tumor cells and delivers a novel protein degrader as a payload to precisely degrade intracellular target proteins, also performing the role of a PROTAC molecule.
Among the groups of CROs, Creative Biolabs is one that can perform both the development of ADC and protein degraders.
Monoclonal antibodies, cytotoxic small compounds, and linkers are the three primary components that may be found in conventional ADC drugs. The small molecule drug is released from the ADC drug by lysosomal degradation once it has bound to the target antigen on the cancer cell. This allows the small molecule drug to kill the cancer cell by either damaging its DNA or preventing it from proliferating.
ADC drugs' tiny compounds are highly effective at destroying cells. They are 100-1000 times as toxic as standard chemotherapeutic drugs. The severe toxicity of free ADC drugs precludes their intravenous injection, however the toxicity of these drugs can be reduced by connecting them to a tumor-specific antibody.
In general, there are two classes of small molecule drugs found in ADC therapies: Inhibitors of microtubule replication (microtubulin inhibitors) cause cells to enter a G2/M arrest and ultimately undergo apoptosis. MMAE, MMAF, and DM1 are all examples of small molecule drugs.
DNA-damaging chemicals attach to the DNA's grooves and trigger cell death. Some examples of drugs in this category are kacinomycin, SN-38, DXd, and PBD, all of which are small molecules.
Intricate planning, precise execution, and exhaustive troubleshooting go into the design of an ADC. The likelihood of a successful ADC can be considerably increased by using a mix of the best possible components.
To begin an ADC development project, antigen selection consultation, antigen-specific antibody screening, internalizing antibody selection, and proof-of-concept feasibility validation utilizing "anti-Ab ADCs" are all part of the antibody screening process. The "chemical warhead" of an ADC is assembled by selecting an appropriate payload drug and then linking it to a linker with the required release mechanism in "DrugLnk," before the antibody is conjugated with it. After ADC assembly, its biochemical characteristics (purity, stability, drug-to-antibody ratio...) and in vitro efficacy are adequately analyzed in ADC in vitro analysis. Prior to clinical evaluation and applications, the ADC's pre-clinical pharmacological parameters will be assayed in ADC in vivo analysis.
Last year, Debiopharm, a Swiss firm, and Ubix Therapeutics, a Korean company, established a research cooperation to create ADeC using the two patented technology platforms MultilinkTM and Degraducer®. This partnership is still in its early stages, and it is possible that the drug in issue has not yet been explored. Nevertheless, it is projected that the ADeC that will be created will be an antibody conjugate drug that substitutes the payload with a degradation molecule, perhaps carrying various payloads for synergistic effects, and so on.
