A look at upregulated targets outside of the BCR signalling pathway and what small molecules are looking promising
In our final preview of ASH 2020 exploring key abstracts and what to watch out for this weekend, we offer the second half of our discussion around small molecules in early stage development.
There’s always a roller coaster ride in any early stage drug development and small molecule inhibitors are no different from antibodies, bispecifics, or even immunotherapies in this respect.
There are certainly some unexpected and surprising overlaps discussed and uncovered here plus also some novel combination approaches either being considered or which may potentially need to be considered in the future.
So what’s in store this time around?
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Molecular biology was a hot new topic back in its infancy in the late 1980’s just as I was finishing my doctorate – cue moment of realising you’ve missed a big wave before it really even started!
Springtime in DC
These days scientists now delve in the realm of deeper molecular biology and go much further than mere genes… it’s all about transcription factors, super enhancers, chromatin complexes, bromodomains, and even chromodomains. In the past, many of these drivers were often considered ‘undruggable’ – think MYC or RAS, for example.
The world of molecular biology is rapidly changing as researchers understand pathways and processes associated with carcinogenesis better, thereby enabling new approaches to evolve and with it, valid new targets for therapeutic intervention.
This field is always one of my favourite ones to cover at AACR, where we not only learn about exciting new research from investigators, but also up and coming young biotech companies that are doing good work who deserve to be highlighted.
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This week certainly turned out to be a defining tale of two drugs with a chequered history…
First off, the FDA approved AbbVie/Genentech’s venetoclax, now known as Venclexta, in a subset of CLL patients with 17p deletions. These patients have a historically poor prognosis and the approval goes some way to addressing the high unmet medical need.
Secondly, another biotech company, Clovis Oncology, got slammed by ODAC with a 12-1 vote to wait for phase 3 data from the TIGER-3 trial for rociletinib to better determine the efficacy:safety benefit profile.
For a long while it seemed that AbbVie had nothing but toil and trouble over the tumour lysis syndrome (TLS) issues giving them some significant challenges to overcome, while Clovis were one of the new darlings of Wall Street.
In the final dash to the market, the tables were turned almost at the 11th hour and fortunes stunningly reversed. Yet a mere eighteen months ago, few industry watchers would have predicted the difference in outcomes.
In our latest AACR Preview series, we take a look at Bcl2 inhibition and where some of the emerging opportunities might lie based on new preclinical research that is being presented here in New Orleans this weekend. It makes for interesting reading.
While one tiger is licking its wounds, another is smacking it chops at what the future might hold for new combination approaches; how the tails have literally turned.
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