In today’s post we answer some reader mailbag questions pertaining to targeting BET/bromodomain inhibitors and what we’ve learned since our original landscape review from early 2016 when they were an emerging new class in the oncology R&D space – how time flies!
Is it time-up for the bromodomain class?
Of course, as usually happens in the targeted therapy space we see a glut of pan inhibitors trying to block everything in sight to a greater or lesser degree… we’ve see this with BRAF, FGFR, PI3K, and even KRAS inhibitors, as well as numerous others, yet these rarely turn out to be the bees knees we’re secretly looking for. Bromodomains, I have long argued, were ripe to fall in this category as well.
Instead, it is better to patiently wait for the next generation molecules where they are much more selective in their actions and matched to the tumour target we are looking to hit.
Think about the BRAFV600E vs. pan BRAF inhibitors or KRASG12C/D vs. pan KRAS inhibitors, for example, or even FGFR2 or FGFR3 vs. pan FGFR inhibitors.
The same evolution may possibly happen in the BET/bromodomain space too.
The first generation of agents seemed to hit everything – BRD1, 2, 3, 4, and often BET as well. They suffered, however, with weak efficacy largely driven by challenges with the on-target, off-tumour effects that necessarily impact the therapeutic window.
Now we are starting to learn from a more focused approach with these agents. Four years on from our original landscape review, what’s hot and what’s not? Who’s in and who’s out? In terms of the magic roundabout of oncology R&D, are there any new gems we should eagerly be watching out for?
The short answer is yes… but what are they and who owns them?
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The BET Bromodomain market is a meaty epigenetics topic we have followed for several years now, including a look at the space back in 2013 on the old Pharma Strategy Blog (Link). The last update on this was ironically at AACR last year when we discussed MYC and bromodomains (Link).
In a remarkable tale of two cities in real life, two companies we discussed in those posts – Constellation Pharma and Tensha Therapeutics – have had markedly different fortunes since then. Roche decided to end their collaboration with the former and went on to acquire the latter instead.
Since we first wrote about bromodomains and BET inhibitors, the niche has exploded in a wildly stunning way… More drugs in the pipeline, more tumour targets being explored, and even novel combinations being evaluated preclinically for synergistic or additive effects. Even I was surprised by how competitive this niche has become based on the offerings at AACR this year.
With all the wealth of new data at the AACR annual meeting and also some other recent presentations I’ve attended elsewhere, it’s time for a more in-depth look at the BET/Bromodomain landscape.
Who are the new players, which tumour targets are now being evaluated, which combinations might be useful?
A word to the wise – this is neither a nerdy science post nor a comprehensive literature review – instead we take a look at the emerging landscape from a new product development perspective.
Science has been absolutely critical to success in all of the cancer therapeutics from targeted therapies to immunotherapies that have emerged in the last decade.
It really doesn’t matter whether you come from a marketing and commercial organisation or the investment community – if you want to make great decisions, you need to understand the basics of the science underpinning the R&D, where the strengths and weaknesses are. The alternative is play Roulette and put everything on Black 11 as a euphemism for whichever company/product/target you have an interest in.
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