Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘BET Bromodomain’

Exciting new developments in the KRAS space

Old Post Office, Barcelona

What started out as a short update from the recent EORTC-NCI-AACR (ENA / Triple Meeting) in Barcelona on new data in the KRAS niche turned out to be a much more in-depth review in light of the explosion of corporate interest in this area.

At this meeting several companies provided updates on compounds, which either recently entered the clinic or were imminent, including the very first KRAS G12D degrader to make it past IND enabling studies. We also saw initial data for many new drugs on the horizon, including some in discovery or preclinical development. There were definitely some gems to be found in the poster hall!

If you didn’t make it to Barcelona for what turned out to be one of the most informative Triple meetings of recent years then this piece is for you if you’re following the burgeoning KRAS space.

In this post we highlight and discuss various direct KRAS approaches, as well as indirect upstream (SHP2), downstream (MEK, ERK, and ULK), and even cross-stream (PI3K) targets of interest.  KRAS G12C inhibitors were just a start, while the future may well look quite different…

To continue reading our latest discussion on oncology new product development plus expert commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

On overcoming resistance to protein degraders

One of the questions we routinely think about at BSB and ask researchers is what are the mechanisms of resistance underlying the therapy they are evaluating in preclinical or clinical studies?

If you understand what these are from the get-go then you can better design rational combination trials to address them and improve outcomes rather than leave things to the vagaries of chance.

In this post, we’re looking at novel approaches researchers are thinking about in relation to resistance with protein degraders and what this may mean for cancer new product development.

Curious to learn more?  Then check out the post below…

To continue reading our latest discussion on oncology new product development plus expert commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

Are we overpromising with protein degraders?

Degrading proteins, block by block

Our KRAS review last week included a lot of different inhibitor compounds (well over 30 of them), illustrating just how complex this niche is rapidly becoming, with only a brief mention of targeted protein degrader (TPD) compounds since these are much further behind their small molecule inhibitor counterparts.

Since then there’s been some more big picture talks or three about the TPD space, which are well worth discussing, as well as a flurry of relevant questions from BSB readers to be addressed.

Here we discuss the KRAS niche in the context of protein degraders and look at the promise and some of the inherent challenges faced…

To continue reading our latest discussion on oncology new product development plus commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

Bigging up targeted therapies at ASH 2020

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?

To learn more from our oncology analysis and get a heads up on the latest insights and commentary pertaining to the ASH meeting — including our final Preview ahead of the meeting this weekend, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

ESMO20 Preview 4 – Targeted therapies to watch out for

Not in Madrid – with the global pandemic continuing to exert a significant effect on the cancer conference season, the annual meetings continue apace virtually.

Plaza de Cibeles, Madrid

For this year’s ESMO meeting we have already covered immunotherapies, both early and late stage pipeline highlights and now it’s time to explore what to watch out for over the weekend on the early to mid stage targeted therapy front.

The good news is there is some potentially practice changing data being presented, as well as some novel approaches in preclinical development emerging. These should be hitting the clinic in the near to medium term future.  On the other extreme is the more common problem whereby a few agents are showing signs of not holding up to their early promise/hype.

Let’s now take a look at what we can learn in the fourth and final ESMO Preview for 2020…

To learn more from our oncology analysis and get a heads up on insights and commentary pertaining to ESMO 2020, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Time is ticking on the bromodomain landscape

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?

To learn more from our oncology analysis and get a heads up on insights emerging the latest trends and commentary subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Novel agents and targets – Part 1

Gems from the poster halls yielded some fascinating novel approaches and new twists on old targets

In this latest post ASH review, we explore some intriguing early developments from several small and large companies alike, explain why they matter and why we should be interested in them.

Sometimes the wisdom of the crowds isn’t always the best indicator of what’s coming down the pike in terms of oncology pipelines.

Part of our cunning plan this year involved going to ‘off Broadway’ sessions where we thought others would skip in favour of a more obviously popular session (the ones in the big halls) and merrily tweet them so you could easily follow along in parallel while the smaller rooms rapidly filled up and quietly closed to those desperately trying to get in late.

Our selections here include several gems from the poster halls (imagine trying to just pick a few highlights out of 4,000 poster options?!), as well as a couple of oral presentations that were missed by many – not surprising given how jam-packed the schedule was with double and even triple choices of selections in parallel to choose from!

Curious to find out more about our latest coverage and get a heads up on additional insights from our post ASH analysis and commentary?Subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Will bromodomain inhibitors and PROTACs make an impact?

Time for some reflection

Before we get to the World Congress in Lung Cancer (WCLC) taking place this weekend, I want to take a moment to reflect on some of the things we have learn over the last few weeks.

It’s time for a reader mailbag as we answer reader questions on the recent MYC mini-series, as well as covering bromodomain inhibitors (what’s going on there?) and discuss a new PROTAC compound in early development that looks quite interesting.

We also explain why that is the case…

To learn more from out latest oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

On the interaction between transcription factors and the immune system

We’re continuing our mini-series on the MYC oncogene and associated super-enhancers and transcription factors, with a look at some of the molecular mechanisms driving epigenetic accessibility and how they interact with the immune system. It turns out that the two appear to be inextricably linked.

Dr Jay Bradner (NIBR)

It’s an exciting and emerging area in oncology R&D as companies and researchers begin to leverage basic science with a convergence between scientific fields to drive new opportunities for therapeutic intervention in cancer.

Included in this post are excerpts from an interview with Dr Jay Bradner from the Novartis Institutes of Biomedical Research. He’s most well known for his academic research on chromatin and bromodomain fields. As Dr Bradner told me during our discussion:

“MYC has so many target genes that I would imagine one might find any number of immune factors as augmented in their expression by MYC.”

As always, we covered a lot of ground and dived into more detail. There’s also been a number of recent research papers published since our discussion that have shed more light on the topic.

This is the second post in our latest mini-series. If you’d liked to read this and our coverage from the forthcoming ESMO, SITC and ASH annual meetings, do sign up to keep up to date…

To learn more from our latest expert interview and get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

A look at the SCLC Landscape and Rova-T

Many of the questions we received from BSB readers this month was a plea from several folks to answer numerous queries about small cell lung cancer (SCLC) and the anti-DLL3 ADC, Rova-T, in particular.

Of course I’m happy to oblige, but this was way too big a topic for inclusion in Friday’s mailbag.

Cornish Tin Mine

What makes a lot more sense here is a short two-part mini series where we look at the dismal landscape of the disease and then consider the red and green flags that arise from the Rova-T development.

With the interim results expected from the phase 2 TRINITY trial in 2H17, this is a timely moment to sit down and reflect on what to expect.

In the first part of the series, we walk through SCLC as a disease, including what is known and what to consider when contemplating a new therapy here.

In the second part tomorrow we will focus more specifically on Rova-T and what to watch out for.

So let’s rock and roll with a look at the SCLC landscape…

To learn more insights on this intriguing topic, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

error: Content is protected !!