Monday, April 29, 2019

Genentech pushes forward with PBDs


https://jhoonline.biomedcentral.com/articles/10.1186/s13045-019-0726-5

Here is a nice summary article about the pursuit of treatments for Acute Myeloid Lukemia.  In it they lay out the best prospects for new therapies and there are two ADCs mentioned which are worth taking a look at.

This CLL target is interesting because it is strongly overexpressed in AML cancer cells, however antibody binding does not illicit an immunogenic effect necessary to use the mAb only therapy as an efficient treatement.

The first is Genentechs labile PBD.  It is described as, "A novel anti–CLL-1-ADC, with a highly potent pyrrolobenzodiazepine (PBD) dimer conjugated through a self-immolative disulfide linker, was developed."
http://clincancerres.aacrjournals.org/content/25/4/1358
https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1517565

Cellerant Therapeutics is also building a very similar molecule which they have called CLT030.
http://www.bloodadvances.org/content/2/14/1738?sso-checked=true
Their molecule is unique in that only targets the stem cells of AML after undergoing the transformation to cancerous, thereby leaving the health HSC cells alone.  Both are showing good results in the xenograft studies, it will be interesting to watch what comes out of the clinic.  Especially because these are both use DNA intercolation as their mechanism of action, and currently PBDs are having a bit of a rough go (see AbbVie's Rova-T)


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