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Yesterday the Danish biotech company announced that it would end the clinical development of its targeted Axl-subject kinase ADC drug enapotamab vedotin.
the drug has shown some efficacy in Phase I clinically, it is also toxic.
and the relationship between efficacy and dosage and biomarkers is not clear enough to meet the criteria for conceptual validation that continue to be developed.
Genmab has many products developed in partnership with large companies, but this product is exclusively owned by Genmab, although its link technology license was acquired from Seagen.
Axl is a polymer kinase that was previously unclear and was once named UFO, but it has recently been found to be associated with many properties of the tumor, such as angiogenes and drug resistance.
but this family kinase is more striking because of its natural immune checkpoint function, and kinases Tyro3 and MERTK are also popular targets for immunotherapy.
is widely expressed, although this makes the anti-cancer spectrum larger but toxic is also a conseidant problem.
in lung cancer Axl mainly in Kras variant subsype overexploitation, but EGFR variant patients after drug resistance also overexploited Axl.
it is estimated that most lung cancer patients may benefit, of course, on the premise that there is sufficient treatment window.
the first phase of the clinical response rate published last year was 19%, but the serious side effect rate was 42%, of which 15% of patients died of toxicity.
Of course ADC failure does not mean that this target fails, relatively mild antibodies may have enough windows because ADC and antibody working mechanisms are quite different, and now Aravive also has a fusion protein drug in the clinic.
other such subject kinase extracellulation, in-cell regulatory effects may be completely different, such as EGFR antibodies and EGFR inhibitors do not have too many crossovers of the adaptation.
if small molecule Axl inhibitors may not require direct contact with tumors from an immunoactivation perspective, the clinical manifestations of small molecule Axl inhibitors may not be similar to lying on this ADC.
is now the leading small molecule Axl inhibitor is Bergenbio's Bemcentinib, also known as the most selective.
of kinase inhibitors has always been an optimization indicator more important than activity, and is particularly important for immunotherapy selectivity.
most of these kinase inhibitors directly interfere with cell growth and division, and now known molecular skeletons come from these traditional targeted drugs.
so any off-target activity is likely to inhibit cell growth, but immunotherapy usually ends up relying on the amplification of killer T-cells.
predictable consequences of poor selectivity, in extreme cases immunosuppression similar to chemotherapy.
Enapotamab vedotin (formerly named HuMax-AXL-ADC, AXL-107-MMAE) antibodies are partly human-specific AXL-specific IgG1, cytotoxalytic for MMAE, and links are peptides that can be hydrolyzed by proteases.
addition to the Axl-targeted ADC drug, Bioatla's BA3011 and ADC's ADCT-601, the current development also seems to encounter some problems, are relatively low-key.
these ADC products although the target is the same but cytotoxyte, link parts are different, so the eye-watcher killing may be different, the efficacy of a safety may also be different.
Axl as a relatively widely expressed target on the ADC a bit of a venture, because ADC is very toxic, simple and rough working, only targeted highly tumor-specific subjects have an advantage.
this year, although the ADC field is frequently reported, but this technology is still relatively demanding.
even Roche said they didn't master the complex technology.
Although ADC technology may not be applicable to most subjects, if antigen expression is highly specific, ADC drugs such as Enhertu, like Maradona on the court, can be the sharpest tumor-killing weapon, a well-deserved No. 10 player.
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